Prediabetes: a high-risk state for diabetes development

May combine two claims.

The reproducibility of prediabetes is about 50%, lower than that for diabetes, which is over 70%.

“The reproducibility of prediabetes (~50%) is lower than that for diabetes (>70%)4 and the alternative definitions based on IFG, IGT and A1c define overlapping prediabetic groups with single or combined abnormalities.”

• cites [4] Balion, 2007, Reproducibility of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) classification: a systematic review, Clin Chem Lab Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Lifestyle modification is the cornerstone of diabetes prevention in prediabetic individuals, with evidence of a 40%-70% relative risk reduction.

“For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction.”

May combine two claims.

Isolated IFG and isolated IGT may define people with different pathophysiological abnormalities, and their combination marks a more advanced disturbance of glycaemic homeostasis.

“Isolated IFG and isolated IGT may define persons with different pathophysiological abnormalities and their combination marks a more advanced disturbance of glycaemic homeostasis.5”

• cites [5] 2003, Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts, Diabetes Care sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Multifactorial risk scores could improve diabetes risk estimation by using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values.

“Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values.”

May combine two claims.

Observational evidence links prediabetes to early nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased macrovascular disease risk.

“Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The prevalence of prediabetes is increasing worldwide.

“The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030.”

May combine two claims.

Prediabetes is associated with simultaneous insulin resistance and β-cell dysfunction, abnormalities that begin before glucose changes are detectable.

“Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Accumulating data suggest potential benefits from pharmacotherapy for prediabetes.

“Accumulating data also suggests potential benefits from pharmacotherapy.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

More than 470 million people are projected to have prediabetes in 2030.

“The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Risk scores for incident diabetes based on a combination of non-invasive or blood-based risk factors are under development to identify individuals at high risk of developing diabetes.

“In addition, risk scores for incident diabetes based on a combination of non-invasive or blood-based risk factors are under development to identify individuals at high risk of developing diabetes.6”

• cites [6] Buijsse, 2011, Risk assessment tools for identifying individuals at risk of developing type 2 diabetes, Epidemiol Rev sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

IFG is more prevalent among men than women.

“In addition, IFG is more prevalent among men than women, although the reasons for this remain poorly understood.10”

• cites [10] Cowie, 2009, Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Increases in glycaemia have resulted in a rise in prediabetes prevalence, although in some populations IGT has not risen despite increasing diabetes incidence.

“Increases in glycaemia have resulted in a rise in prediabetes prevalence, although in some populations IGT has not risen despite increasing diabetes incidence, probably because increases in obesity influence FPG more than 2-h glucose and because of improved detection of diabetes.8”

• cites [8] Katikireddi, 2011, Is there a divergence in time trends in the prevalence of impaired glucose tolerance and diabetes? A systematic review in south Asian populations, Int J Epidemiol sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Applying those percentages to the entire U.S. population in 2010 yields an estimated 79 million adults with prediabetes.

“Applying these percentages to the entire U.S. population in 2010 yields an estimated 79 million adults with prediabetes.9”

• cites [9] 2011Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Oceania had the highest mean FPG of any region, at 6.1 mmol/L for men and women.

“Oceania had the highest mean FPG of any region (6.1 mmol/L for men and women), but mean FPG was also high in some other regions (South and Central Asia, Latin America, the Carribean, North Africa, and the Middle East).7”

• cites [7] Danaei, 2011, National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In 2008, age-standardised mean fasting plasma glucose was 5.5 mmol/L in men and 5.4 mmol/L in women, a rise of 0.1 mmol/L since 1980.

“According to pooled data from 2.7 million adults participating in health surveys and epidemiological studies, age-standardised mean fasting plasma glucose (FPG) was 5.5 mmol/L in men and 5.4 mmol/L in women in 2008, a rise of 0.1 mmol/L since 1980.”

• cites [7] Danaei, 2011, National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

NHANES 2005-2008 suggests that 35% of U.S. adults over 20 years of age and 50% of those over 65 had prediabetes based on fasting glucose or A1c levels.

“The population-based U.S. National Health and Nutrition Examination Survey (NHANES) suggests that 35% of U.S. adults over 20 years of age and 50% of those over 65 had prediabetes in 2005–2008 based on fasting glucose or A1c levels.9”

• cites [9] 2011Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The prevalences of IFG and IGT vary between ethnic groups and both conditions are more common in older people.

“The prevalences of IFG and IGT vary between ethnic groups and both conditions are more common in older people.10”

• cites [10] Cowie, 2009, Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Recent major studies found annualised diabetes incidence of 11% in the DPP Outcomes Study, 6% among MESA participants with IFG, 9% among Japanese participants with IFG, and 7% among those with A1c 5.7-6.4%.

“In more recent major studies, progression estimates have been similar: the annualised incidence was 11% in the Diabetes Prevention Program (DPP) Outcomes Study,15 6% among participants with IFG in the US Multi-Ethnic Study of Atherosclerosis (MESA),16 9% among participants with IFG and 7% among those with an A1c 5.7–6.4% in a Japanese population-based study.17”

• cites [15] 2009, 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [16] Yeboah, 2011, Impaired fasting glucose and the risk of incident diabetes mellitus and cardiovascular events in an adult population: MESA (Multi-Ethnic Study of Atherosclerosis), J Am Coll Cardiol sourceNot checked yet

  Not checked in the free run.

• cites [17] Heianza, 2011, HbA1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In a meta-analysis of 20 studies, 13% of mothers with gestational diabetes developed diabetes after pregnancy compared with 1% of mothers without gestational diabetes.

“In a recent meta-analysis of 20 studies, 13% of mothers with gestational diabetes developed diabetes after pregnancy compared to 1% of mothers without gestational diabetes.23”

• cites [23] Bellamy, 2009, Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The number of adults with IGT is expected to increase globally, reaching 472 million by 2030.

“The number of adults with IGT is expected to increase globally, reaching 472 million by 2030.”

• cites [11] 2011Not checked yet

  Not checked in the free run.

May combine two claims.

In a meta-analysis of prospective studies published up to 2004, annualised incidence rates of diabetes were 4-6% for isolated IGT, 6-9% for isolated IFG, and 15-19% for IFG and IGT combined.

“In a meta-analysis of prospective studies published up to 2004, annualised incidence rates of diabetes for isolated IGT (4–6%) and isolated IFG (6–9%) were lower than those for IFG and IGT combined (15–19%).14”

• cites [14] Gerstein, 2007, Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies, Diabetes Res Clin Pract sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The greatest absolute rises in IGT are expected in South-East Asia and the Western Pacific Region.

“The greatest absolute rises are expected in South-East Asia and the Western Pacific Region.11”

• cites [11] 2011Not checked yet

  Not checked in the free run.

May combine two claims.

Around 5-10% of people with prediabetes become diabetic annually, although conversion rate varies by population characteristics and definition of prediabetes.

“Around 5–10% of people with prediabetes become diabetic annually although conversion rate varies by population characteristics and the definition of prediabetes.12,13”

• cites [12] Forouhi, 2007, Incidence of type 2 diabetes in England and its association with baseline impaired fasting glucose: the Ely study 1990–2000, Diabet Med sourceNot checked yet

  Not checked in the free run.

• cites [13] Nathan, 2007, Impaired fasting glucose and impaired glucose tolerance: implications for care, Diabetes Care sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

A two-stage process using non-invasive parameters first and laboratory measures second could efficiently estimate diabetes risk.

“In clinical practice, a two-stage process could be efficient: diabetes prediction models with non-invasive parameters such as age, sex, BMI, blood pressure, diabetes family history and lifestyle information allow a first assessment of diabetes risk with little effort and costs.”

May combine two claims.

There is no single universally accepted diabetes prediction model, and recalibration may be necessary when prediction algorithms are applied to different populations because ethnicity is strongly related to diabetes risk.

“There is no single universally accepted diabetes prediction model and given that ethnicity is strongly related to diabetes risk, recalibration of prediction algorithms may be necessary when they are applied to different populations.30”

• cites [30] Noble, 2011, Risk models and scores for type 2 diabetes: systematic review, BMJ sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In healthy people, fasting glucose is maintained between 3.9 and 5.6 mmol/L and post-meal increases rarely exceed 3 mmol/L.

“Fasting glucose is maintained between 3.9 and 5.6 mmol/L37 and the post-meal increases rarely exceed 3 mmol/L.38”

• cites [37] Abdul-Ghani, 2006, Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [38] Ferrannini, 2011, Pathophysiology of prediabetes, Med Clin North Am sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the Whitehall II study, people who developed diabetes had increased glucose values 13 years before diagnosis, with glucose tightly regulated within the normal range until 2-6 years before diagnosis, when an abrupt increase occurred.

“In people who developed diabetes, increased glucose values were observed already at the beginning of the follow-up, 13 years before diagnosis, although glucose values seemed to be tightly regulated within the normal range until 2–6 years before diagnosis when an abrupt increase was found.”

• cites [36] Tabák, 2009, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The first stage of diabetes development is a long compensatory period when insulin resistance is present and accompanied by increased rates of insulin secretion and increased β-cell mass.

“The first stage of diabetes development is a long compensatory period when insulin resistance is present and accompanied by increased rates of insulin secretion44 and an increased β-cell mass.39”

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [44] Polonsky, 1988, Quantitative study of insulin secretion and clearance in normal and obese subjects, J Clin Invest sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The second stage is the stable adaptation period when β-cells are no longer fully compensating for increased insulin resistance, so fasting and/or postload glucose values are not completely maintained.

“The second stage is the stable adaptation period when β-cells are no longer fully compensating for increased insulin resistance; thus fasting and/or postload glucose values are not completely maintained.”

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [43] Weir, 2004, Five stages of evolving beta-cell dysfunction during progression to diabetes, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In Whitehall II, insulin secretion was elevated throughout the 13-year observation period, increased markedly 4-3 years before diagnosis, and then steeply decreased until diagnosis.

“Insulin secretion was elevated throughout the 13-year observation period and showed a marked increase 4-3 years before diagnosis, followed by a steep decrease until diagnosis.36”

• cites [36] Tabák, 2009, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In Whitehall II, insulin sensitivity was reduced 13 years before diabetes onset, with a steeper decline 5 years before diagnosis.

“Figure 2 shows that insulin sensitivity was reduced already 13 years before the onset of diabetes, with a steeper decline observed 5 years before diagnosis.”

• cites [36] Tabák, 2009, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Insulin resistance starts years before diabetes development and decreased beta-cell function is already present in the prediabetic stage.

“This is in line with the notion that insulin resistance starts years before diabetes development and that decreased beta-cell function is already present in the prediabetic stage.37,42”

• cites [37] Abdul-Ghani, 2006, Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [42] Gastaldelli, 2004, Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study, Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The second stage likely starts when fasting and postload glucose levels are within the normal range and is usually accompanied by a decrease in acute insulin secretion at FPG levels around 5.6 mmol/L.

“This period is likely to start when fasting and postload glucose levels are within the normal range36,39,43 and is usually accompanied by a decrease in acute insulin secretion that is present at FPG levels around 5.6 mmol/L.39”

• cites [36] Tabák, 2009, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [43] Weir, 2004, Five stages of evolving beta-cell dysfunction during progression to diabetes, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The relation between insulin secretion and insulin sensitivity is hyperbolic, and the disposition index is a measure of insulin secretion after accounting for the underlying degree of insulin resistance.

“According to this concept, the relation between insulin secretion and insulin sensitivity is hyperbolic; the ratio of incremental insulin over incremental glucose divided by insulin resistance is described by a constant, the disposition index.39,47”

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [47] Kahn, 2003, The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes, Diabetologia sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

By definition, β-cell dysfunction is already present in the prediabetic phase.

“This means that, by definition, β-cell dysfunction is already present in the prediabetic phase.”

May combine two claims.

The product of endogenous glucose production and fasting insulin is used as a marker of hepatic insulin resistance and shows a relatively strong relationship with fasting glycaemia.

“The product of EGP and fasting insulin is used as a marker of hepatic insulin resistance and it shows a relatively strong relationship with fasting glycaemia.38,39,45”

• cites [38] Ferrannini, 2011, Pathophysiology of prediabetes, Med Clin North Am sourceNot checked yet

  Not checked in the free run.

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [45] DeFronzo, 2011, Preservation of beta-cell function: the key to diabetes prevention, J Clin Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In type 2 diabetes, total body glucose disposal is decreased and 85-90% of this impairment is related to muscle insulin resistance.

“In type 2 diabetes, total body glucose disposal is also decreased and 85–90% of this impairment is related to muscle insulin resistance.46”

• cites [46] Pendergrass, 2007, Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals, Am J Physiol Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The third stage is the unstable early decompensation period, when β-cells become unable to compensate for insulin resistance and glucose levels start to increase rapidly.

“During the unstable early decompensation period, the third stage of diabetes development, the β-cells become unable to compensate for a given insulin resistance and consequently glucose levels start to increase rapidly39,43 as it was seen in Whitehall II and other longitudinal studies.36,41”

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [43] Weir, 2004, Five stages of evolving beta-cell dysfunction during progression to diabetes, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [36] Tabák, 2009, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [41] Mason, 2007, Progression to type 2 diabetes characterized by moderate then rapid glucose increases, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Both IFG and IGT subjects present with insulin resistance, but the site differs: IFG has high hepatic insulin resistance with almost normal skeletal muscle values, while IGT has main insulin resistance in muscle with only modest changes in liver insulin sensitivity.

“Both IFG and IGT subjects present with insulin resistance, however the site of insulin resistance is different: High hepatic insulin resistance is a typical finding in IFG with almost normal values in skeletal muscle.38,39,45 In IGT, the main site of insulin resistance is the muscle with only modest changes in liver insulin sensitivity.37,38”

• cites [37] Abdul-Ghani, 2006, Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [38] Ferrannini, 2011, Pathophysiology of prediabetes, Med Clin North Am sourceNot checked yet

  Not checked in the free run.

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [45] DeFronzo, 2011, Preservation of beta-cell function: the key to diabetes prevention, J Clin Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Subjects with isolated IFG and isolated IGT differ in their fasting and 2-h postload glucose values and by the shape of the glucose concentration curves during the OGTT.

“Subjects with isolated IFG and isolated IGT differ in their fasting and 2-h postload glucose values and by the shape of the glucose concentration curves during the OGTT.”

May combine two claims.

β-cell dysfunction is present in both isolated IFG and isolated IGT; IFG people have severely impaired early insulin response during OGTT but improve in the second phase, while IGT people have impaired early and late phase insulin secretion.

“β-cell dysfunction is present both in people with isolated IFG and isolated IGT. IFG people have severely impaired early insulin response during OGTT but their insulin secretion improves during the second phase of the OGTT. In contrast, IGT people present with impaired early and late phase insulin secretion.38,39,50”

• cites [38] Ferrannini, 2011, Pathophysiology of prediabetes, Med Clin North Am sourceNot checked yet

  Not checked in the free run.

• cites [39] DeFronzo, 2009, Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes sourceNot checked yet

  Not checked in the free run.

• cites [50] Kanat, 2012, Distinct beta-cell defects in impaired fasting glucose and impaired glucose tolerance, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The strongest supportive evidence for prediabetes-related neuropathy relates to autonomic neuropathy, although the method of detection seems to be critical.

“Neuropathies can be further divided into subcategories; the strongest supportive evidence relates to autonomic neuropathy, although the method of detection seems to be critical.”

May combine two claims.

Prediabetes has been found to be associated with decreased heart rate variability, decreased postural changes in heart rate, increased prevalence of erectile dysfunction among men, and a worse profile in tests of sympathetic and parasympathetic function.

“Prediabetes has been found to be associated with decreased heart rate variability61 (HRV – a marker of parasympathetic function),62–65, decreased postural changes in heart rate,62 increased prevalence of erectile dysfunction among men,66 and a worse profile in tests of sympathetic and parasympathetic function.67”

• cites [61] Tesfaye, 2010, Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [62] Wu, 2007, Epidemiological evidence of altered cardiac autonomic function in subjects with impaired glucose tolerance but not isolated impaired fasting glucose, J Clin Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

• cites [63] Gerritsen, 2000, Glucose tolerance and other determinants of cardiovascular autonomic function: the Hoorn Study, Diabetologia sourceNot checked yet

  Not checked in the free run.

• cites [64] Singh, 2000, Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study), Am J Cardiol sourceNot checked yet

  Not checked in the free run.

• cites [65] Schroeder, 2005, Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [66] Grover, 2006, The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease, Arch Intern Med sourceNot checked yet

  Not checked in the free run.

• cites [67] Putz, 2009, Noninvasive evaluation of neural impairment in subjects with impaired glucose tolerance, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Longitudinal studies suggest that prediabetes is a risk factor for subsequent CKD, but it is unclear whether this prospective association is attributable to prediabetes itself, increased incidence of diabetes, or common causes.

“Longitudinal studies suggest that prediabetes is a risk factor for subsequent CKD but it is unclear whether this prospective association is attributable to the effects of prediabetes itself, increased incidence of diabetes, or common causes contributing to both hyperglycaemia and kidney pathology.59,60”

• cites [59] Fox, 2005, Glycemic status and development of kidney disease: the Framingham Heart Study, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [60] Thomas, 2011, Metabolic syndrome and kidney disease: a systematic review and meta-analysis, Clin J Am Soc Nephrol sourceNot checked yet

  Not checked in the free run.

May combine two claims.

No consistent evidence is available to suggest that prediabetes is associated with measurements of orthostatic blood pressure changes or with decreased expiratory-inspiratory ratio or change in heart rate during breathing.

“No consistent evidence is available to suggest that prediabetes is associated with measurements of orthostatic blood pressure changes,63 which is a late marker of diabetic neuropathy,61 or with decreased expiratory-inspiratory ratio or change in heart rate during breathing.63”

• cites [61] Tesfaye, 2010, Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [63] Gerritsen, 2000, Glucose tolerance and other determinants of cardiovascular autonomic function: the Hoorn Study, Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Prediabetes status may be associated with an increased risk of diabetic retinopathy, although findings vary depending on the method of detection.

“Prediabetes status may be associated with an increased risk of diabetic retinopathy although the findings vary depending on the method of detection.51,79–83”

• cites [51] Gabir, 2000, Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [79] Algvere, 1985, Retinal microangiopathy and pigment epithelial lesions in subjects with normal, borderline, and decreased oral glucose tolerance, Br J Ophthalmol sourceNot checked yet

  Not checked in the free run.

• cites [80] Tapp, 2008, Longitudinal association of glucose metabolism with retinopathy: results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [81] Nguyen, 2007, Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [82] Wong, 2002, Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons, JAMA sourceNot checked yet

  Not checked in the free run.

• cites [83] Nguyen, 2008, Retinal arteriolar narrowing predicts incidence of diabetes: the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Evidence is accumulating on increased prevalence of idiopathic polyneuropathy among prediabetic individuals, with IGT being more strongly related to painful than non-painful neuropathy.

“Finally, evidence is accumulating on increased prevalence of idiopathic polyneuropathy (eg, idiopathic sensory/painful neuropathy,73–78 and sensory/small fibre only neuropathy)73,75,78 among prediabetic individuals with IGT being more strongly related to painful than non-painful neuropathy.73,75,78”

• cites [73] Hoffman-Snyder, 2006, Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy, Arch Neurol sourceNot checked yet

  Not checked in the free run.

• cites [74] Smith, 2004, The diagnostic yield of a standardized approach to idiopathic sensory-predominant neuropathy, Arch Intern Med sourceNot checked yet

  Not checked in the free run.

• cites [75] Singleton, 2001, Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [76] Nebuchennykh, 2008, Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series, Eur J Neurol sourceNot checked yet

  Not checked in the free run.

• cites [77] Smith, 2001, Epidermal nerve innervation in impaired glucose tolerance and diabetes-associated neuropathy, Neurology sourceNot checked yet

  Not checked in the free run.

• cites [78] Sumner, 2003, The spectrum of neuropathy in diabetes and impaired glucose tolerance, Neurology sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Prediabetes is linked with increased risks of major manifestations of vascular disease, but it remains unclear whether the elevated disease risks depend on development of clinical diabetes.

“Prediabetes is linked with increased risks of major manifestations of vascular disease, but it remains unclear whether the elevated disease risks depend on development of clinical diabetes.84,85”

• cites [84] 2010, Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [85] Seshasai, 2011, Diabetes mellitus, fasting glucose, and risk of cause-specific death, N Engl J Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Measures of retinal vascular changes, such as lower arteriole-to-venule ratio and increased retinal arteriole or venular calibre, have been shown to be related to prediabetes or increased risk of diabetes, but the evidence is not entirely consistent.

“Measures of retinal vascular changes, such as lower arteriole-to-venule ratio, increased retinal arteriole or venular calibre, have also been shown to be related to prediabetes or increased risk of diabetes, but the evidence is not entirely consistent.81–83”

• cites [81] Nguyen, 2007, Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [82] Wong, 2002, Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons, JAMA sourceNot checked yet

  Not checked in the free run.

• cites [83] Nguyen, 2008, Retinal arteriolar narrowing predicts incidence of diabetes: the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Average glucose levels indexed by HbA1c predict incident coronary disease at least as well as fasting and postload glucose, though there are comparatively few prospective studies of HbA1c.

“Whether it is the basal or the challenged blood glucose level that is more important for atherogenesis, average glucose levels, indexed by HbA1c concentration, predict incident coronary disease at least as well as fasting and postload glucose, though there are comparatively few prospective studies of HbA1c.89”

• cites [89] Sarwar, 2010, Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review, PLoS Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Cross-sectional studies argue in favour of vascular risk effects of mild or moderate hyperglycaemia, as there is an excess prevalence of coronary disease in those with fasting or postload hyperglycaemia below the diabetic level.

“Cross-sectional studies argue in favour of vascular risk effects of mild or moderate hyperglycaemia as there is an excess prevalence of coronary disease in those with fasting or postload hyperglycaemia below the diabetic level.86,87”

• cites [86] Barr, 2007, Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), Circulation sourceNot checked yet

  Not checked in the free run.

• cites [87] Brunner, 2006, Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study, Diabetes Care sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diabetes is a known risk factor for ischaemic and haemorrhagic stroke, but it remains to be established whether risk increases before development of diabetes.

“Diabetes is a known risk factor for ischaemic and haemorrhagic stroke, but it remains to be established whether risk increases before development of diabetes. 84”

• cites [84] 2010, Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The DECODE pooling study found IGT to be associated with increased risk of coronary death and total cardiovascular death, independent of the level of FPG, while the converse was not the case.

“The DECODE pooling study of European cohorts found IGT to be associated with increased risk of coronary death and total cardiovascular death, independent of the level of FPG, while the converse was not the case.88”

• cites [88] 2001, Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria, Arch Intern Med sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Evidence is accumulating to demonstrate potential benefits from pharmacotherapy for prediabetes.

“Evidence is also accumulating to demonstrate potential benefits from pharmacotherapy.”

Classified as probably not a substantial claim.

The majority of studies in this field support the concept that lifestyle change should be the cornerstone for diabetes prevention.

“Majority of the studies in this field of research have focused on diabetes incidence among prediabetic individuals and support the concept that lifestyle change should be the cornerstone for diabetes prevention.”

May combine two claims.

In the Finnish trial, benefits depended on the number of goals achieved by the participant; in the DPP, each 1-kg decrease in weight reduced diabetes risk by 16%.

“In the first trial, the benefits were dependent on the number of goals achieved by the participant (weight reduction >5%, fat intake< 30%, saturated fat intake < 10%, fiber intake >15g/1000 kcal, exercise > 4h/week),28 while in the DPP the most important determinant of risk reduction was weight loss (each 1-kg decrease reduced the risk by 16%).90”

• cites [28] Tuomilehto, 2001, Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance, N Engl J Med sourceNot checked yet

  Not checked in the free run.

• cites [90] Hamman, 2006, Effect of weight loss with lifestyle intervention on risk of diabetes, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Recent individual-level evidence from prospective studies suggests that fasting hyperglycaemia, postload glucose, and A1c are all robust predictors of vascular mortality, and multivariable adjusted analyses indicate these associations are independent of vascular risk factors such as obesity, blood pressure, triglyceride and lipoproteins.

“A recent individual-level evidence from prospective studies suggests that fasting hyperglycaemia (figure 3), postload glucose, and A1c are all robust predictors of vascular mortality86,88,89 and, according to multivariable adjusted analyses, these associations are independent of vascular risk factors, such as obesity, blood pressure, triglyceride and lipoproteins.84,85,87”

• cites [84] 2010, Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [85] Seshasai, 2011, Diabetes mellitus, fasting glucose, and risk of cause-specific death, N Engl J Med sourceNot checked yet

  Not checked in the free run.

• cites [87] Brunner, 2006, Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [88] 2001, Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria, Arch Intern Med sourceNot checked yet

  Not checked in the free run.

• cites [89] Sarwar, 2010, Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review, PLoS Med sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Reasons for treating prediabetes include prevention of progression to diabetes, mitigation of some potential consequences of progression to diabetes, and prevention of potential consequences of prediabetes itself.

“The reasons for treating prediabetes include prevention of progression to diabetes, mitigation of some of the potential consequences of progression to diabetes as well as prevention of the potential consequences of prediabetes itself.”

May combine two claims.

Rosiglitazone was effective in a 3-year randomised trial showing a 60% reduction in incident diabetes risk, but it was associated with significant weight increase of about 2 kg compared to placebo and increased risk of heart failure (0.1% vs 0.5% in controls).

“Rosiglitazone was effective in a 3-year randomised trial that showed a 60% reduction in incident diabetes risk but this drug was also associated with significant weight increase (~2 kg compared to placebo) and increased risk of heart failure (0.1% vs. 0.5% in controls).24,97”

• cites [24] 2006, Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [97] Dagenais, 2008, Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Pioglitazone showed effectiveness in the ACT NOW Study on obese people with IGT: diabetes risk decreased by over 70%, with improved diastolic blood pressure, improved HDL-cholesterol, and reduced carotid intima-media thickening, but greater weight gain (~3 kg) and more frequent edema (13% vs 6%).

“Pioglitazone showed effectiveness in the ACT NOW Study on obese people with IGT. The risk of diabetes decreased by >70% and the drug was associated with improved diastolic blood pressure, improved HDL-cholesterol and a reduced rate of carotid intima-media thickening. However, weight gain was greater with pioglitazone (~3 kg compared to placebo) and edema was more frequently reported (13% vs. 6%).”

• cites [29] DeFronzo, 2011, Pioglitazone for diabetes prevention in impaired glucose tolerance, N Engl J Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Metformin has beneficial effects on BMI and lipid levels and has been proven safe based on trial evidence showing no serious adverse effects, only minor gastrointestinal side effects.

“Metformin, used for decades to treat diabetes, has beneficial effects on BMI and lipid levels and has been proven to be safe based on trial evidence showing that there were no serious adverse effects (only minor gastrointestinal side effects were detected).94”

• cites [94] Salpeter, 2008, Meta-analysis: metformin treatment in persons at risk for diabetes mellitus, Am J Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Glitazones such as troglitazone, rosiglitazone, and pioglitazone act through the PPAR-γ receptor by increasing hepatic and peripheral insulin sensitivity and preserving insulin secretion.

“The glitazones, such as troglitazone, rosiglitazone and pioglitazone, act through the PPAR-γ receptor by increasing hepatic and peripheral insulin sensitivity and preserving insulin secretion.45,95”

• cites [45] DeFronzo, 2011, Preservation of beta-cell function: the key to diabetes prevention, J Clin Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

• cites [95] Nathan, 2009, Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes, Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Successful lifestyle interventions seem to improve insulin sensitivity and β-cell function.

“Successful lifestyle interventions seem to improve insulin sensitivity and β-cell function.92,93”

• cites [92] Snehalatha, 2009, Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1), Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [93] Kitabchi, 2005, Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin, Diabetes sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Gastrointestinal side effects of metformin were mostly mild to moderate, so the intervention seemed to be safe.

“Gastrointestinal side effects of the drug were mostly mild to moderate, so the intervention seemed to be safe.25,26”

• cites [25] Knowler, 2002, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N Engl J Med sourceNot checked yet

  Not checked in the free run.

• cites [26] Ramachandran, 2006, The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1), Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Metformin's effect was similar to lifestyle intervention in the Indian DPP-1 study, while in the US DPP it was less effective than lifestyle.

“Its effect was similar to lifestyle intervention in the Indian DPP-1 study,26 while in the US DPP it was less effective than lifestyle.25”

• cites [25] Knowler, 2002, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N Engl J Med sourceNot checked yet

  Not checked in the free run.

• cites [26] Ramachandran, 2006, The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1), Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Two large trials support the effectiveness of α-glucosidase inhibitors in the prevention of diabetes, and one of them also shows evidence of decreased CVD and hypertension risk among treated IGT patients.

“However, two large trials support the effectiveness of these drugs in the prevention of diabetes and importantly one of them also shows evidence of decreased CVD and hypertension risk among treated IGT patients.102,103”

• cites [102] Kawamori, 2009, Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [103] Chiasson, 2002, Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

α-glucosidase inhibitors reduce the rate of polysaccharide digestion from the proximal small intestine and primarily lower postprandial glucose without causing hypoglycaemia.

“α-glucosidase inhibitors reduce the rate of polysaccharide digestion from the proximal small intestine. They primarily lower postprandial glucose without causing hypoglycaemia.”

• cites [95] Nathan, 2009, Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes, Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Troglitazone was withdrawn from the European market for probable serious hepatotoxicity, and rosiglitazone for possible increases in cardiovascular risk.

“Two thiazolidinedione drugs were withdrawn from the European market, troglitazone for probable serious hepatotoxicity, and rosiglitazone due to possible increases in cardiovascular risk.45,95”

• cites [45] DeFronzo, 2011, Preservation of beta-cell function: the key to diabetes prevention, J Clin Endocrinol Metab sourceNot checked yet

  Not checked in the free run.

• cites [95] Nathan, 2009, Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes, Diabetologia sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

There is some suggestion of a possible link between pioglitazone and bladder cancer, so individuals with a history of bladder cancer or unexplained hematuria should probably not receive this drug.

“There is also some suggestion of a possible link between pioglitazone and bladder cancer and therefore individuals with a history of bladder cancer or unexplained hematuria should probably not receive this drug.98,99”

• cites [98] Piccinni, 2011, Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [99] Tseng, 2012, Pioglitazone and bladder cancer: a population-based study of Taiwanese, Diabetes Care sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the STOP-NIDDM trial, a 25% relative risk reduction for diabetes was found among people with IGT randomised to acarbose 100 mg t.i.d. or identical placebo during 3.3 years of follow-up, but almost one third of the acarbose group could not complete the trial because of gastrointestinal side effects.

“In the STOP-NIDDM trial, a 25% relative risk reduction for diabetes was found among people with IGT who were randomised to either acarbose 100 mg t.i.d. or identical placebo during 3.3 years of follow-up,103,104 but almost one third of the acarbose group could not complete the trial because of gastrointestinal side effects, such as flatulence and diarrhoea.103”

• cites [103] Chiasson, 2002, Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [104] Chiasson, 2003, Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial, JAMA sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Exenatide and liraglutide were both found to produce sustained weight loss among obese subjects and were associated with increased reversion from prediabetes to normoglycaemia over 1-2 years of follow-up, with nausea and vomiting as the most frequent side effects.

“Exenatide and liraglutide were both found to produce sustained weight loss among obese subjects and were associated with increased reversion from prediabetes to normoglycaemia over 1–2 years of follow-up. The most frequent side effects were nausea and vomiting in these studies.105–107”

• cites [105] Astrup, 2011, Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide, Int J Obes (Lond)Not checked yet

  Not checked in the free run.

• cites [106] Rosenstock, 2010, Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes, Diabetes Care sourceNot checked yet

  Not checked in the free run.

• cites [107] Astrup, 2009, Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the CANOE trial, low doses of rosiglitazone in combination with metformin reduced incident diabetes risk by 66% with no significant difference in weight gain compared to controls, but more people complained of diarrhoea in the active treatment group (16% vs 6%).

“In the recently published CANOE trial, low doses of rosiglitazone (2 mg b.i.d.) in combination with metformin were tested against placebo to examine whether the lower doses would cause less side effects. The risk of incident diabetes was reduced by 66% in the active treatment group with no significant difference in weight gain as compared to controls. However more people complained of diarrhoea in”

• cites [101] Zinman, 2010, Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

A recent study investigating voglibose found a 40% reduction in incident diabetes risk over 48 weeks of follow-up among high-risk Japanese individuals with IGT, with gastrointestinal side effects similar to previous trials but more people completing the study.

“A recent study investigating voglibose, another α-glucosidase inhibitor, found a 40% reduction in incident diabetes risk over 48 weeks of follow-up among high-risk Japanese individuals with IGT. Although the gastrointestinal side effects were similar as reported in previous trials, more people completed that study.102”

• cites [102] Kawamori, 2009, Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In light of current evidence, the effect of ACE inhibitors and ARBs on diabetes is much smaller than that of antidiabetic drugs, and they are not recommended for the treatment of prediabetes.

“In light of current evidence, the effect of these drugs is much smaller than that of the antidiabetic drugs and they are not recommended for the treatment of prediabetes.”

• cites [111] Al-Mallah, 2010, Do angiotensin converting enzyme inhibitors or angiotensin receptor blockers prevent diabetes mellitus? A meta-analysis, Cardiol JNot checked yet

  Not checked in the free run.

• cites [112] McMurray, 2010, Effect of valsartan on the incidence of diabetes and cardiovascular events, N Engl J Med sourceNot checked yet

  Not checked in the free run.

• cites [113] Bosch, 2006, Effect of ramipril on the incidence of diabetes, N Engl J Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In a post hoc analysis of obese people, orlistat was associated with greater weight loss (6.7 vs 3.8 kg) compared to placebo and a significantly reduced conversion from IGT to diabetes (7.6% vs 3.0%) in a 1.5-year follow-up.

“In a post hoc analysis of obese people, this drug was associated with greater weight loss (6.7 vs. 3.8 kg) compared to placebo with a significantly reduced conversion from IGT to diabetes (7.6% vs. 3.0%) in a 1.5-year follow-up.109”

• cites [109] Heymsfield, 2000, Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults, Arch Intern Med sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Lifestyle and drug-based interventions lower the long-term risk of diabetes or postpone its onset.

“Several trials support a long-term reduction in diabetes risk or a delay in the onset of the disease as a result of lifestyle and drug-based interventions.15,19,116–118”

• cites [15] 2009, 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [19] Li, 2008, The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [116] Hopper, 2011, Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled clinical trials, Eur J Cardiovasc Prev Rehabil sourceNot checked yet

  Not checked in the free run.

• cites [117] Lindström, 2006, Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [118] Gerstein, 2011, Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes, Diabetologia sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The 4-year XENDOS trial reported a 37% reduction in relative risk of diabetes among obese people treated with orlistat, although only 52% completed treatment compared with 34% of placebo recipients; an explanatory analysis suggested the preventive effect was mainly confined to subjects with IGT.

“This finding is consistent with the 4-year XENDOS trial that reported a 37% reduction in relative risk of diabetes among obese people treated with orlistat although in that study only 52% completed treatment compared with 34% of placebo recipients. An explanatory analysis suggested that the preventive effect was mainly confined to subjects with IGT.27”

• cites [27] Torgerson, 2004, XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients, Diabetes Care sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The review searched Pubmed from inception to January 2012 using specified terms for each section, and also searched reference lists.

“We searched Pubmed (from inception to January 2012).”

May combine two claims.

A meta-analysis of trials in prediabetic people found that lifestyle and drug-based interventions did not significantly affect all-cause mortality or cardiovascular death over a mean 3.8 years, except for a borderline reduction in stroke risk.

“In a recent meta-analysis of trials among prediabetic people, lifestyle and drug-based interventions had no significant effect on the risk of all-cause mortality or cardiovascular death during the mean follow-up of 3.8 years, except for a borderline significant reduction in stroke risk.116”

• cites [116] Hopper, 2011, Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled clinical trials, Eur J Cardiovasc Prev Rehabil sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable).

Population-wide approaches must be supplemented by prevention efforts targeted at prediabetic and other high-risk people.

“our seminar has shown that these need to be complemented with diabetes prevention strategies based on interventions specifically aimed at prediabetic and other high-risk individuals.”

May combine two claims.

Randomized trials show that lifestyle intervention and several antidiabetic drugs are effective in preventing diabetes.

“Based on randomized trials that show the effectiveness of lifestyle intervention and several antidiabetic drugs in the prevention of diabetes”

May combine two claims.

Prediabetes is linked to a higher likelihood of diabetes and its complications.

“Prediabetes is not only related to an increased risk of diabetes and its complications”

• AssumptionRests on an assumption: The prediabetes concept denotes a varied patient group marked by concurrent insulin resistance and β-cell dysfunction.

May combine two claims.

At 20 years in the DaQing Diabetes Prevention Study, lifestyle intervention cut diabetes risk by 43% and postponed onset by an average of 3.6 years.

“In the 20-year follow-up of the DaQing Diabetes Prevention Study, for example, those receiving a lifestyle intervention had a 43% reduced risk of diabetes, translating to a mean 3.6 year delay in the development of diabetes.119”

• cites [119] Gong, 2011, Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study, Diabetologia sourceNot checked yet

  Not checked in the free run.