Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance

Lifestyle interventions and weight loss reverse T2DM in early stages when insulin is still secreted, but patients may become dependent on anti-diabetic drugs in later stages.

“Although lifestyle interventions393 and weight loss394 reverse T2DM in early stages, when insulin is still secreted, T2DM patients may become dependent on anti-diabetic drugs in later stages.”

In four of the five clinical trials, diabetes rates decreased in relation to substantial reductions in body weight, whereas in the Indian trial lifestyle intervention was successful despite no weight loss.

“In four of these studies ( 2 – 5 ), diabetes rates decreased in relation to substantial reductions in body weight, whereas in the Indian trial ( 6 ) lifestyle intervention was successful despite no weight loss.”

Lifestyle modification in the Finnish Diabetes Prevention Study and the U.S. Diabetes Prevention Program reduced incident diabetes by 58% and, in the DPP, had a greater effect than metformin (31%).

“Lifestyle modification in both studies reduced incident diabetes by 58% and, in the DPP, had a greater effect than metformin (31%).”

The most robust research available related to eating patterns for prediabetes or type 2 diabetes prevention are Mediterranean-style, low-fat, or low-carbohydrate eating plans.

“The most robust research available related to eating patterns for prediabetes or type 2 diabetes prevention are Mediterranean-style, low-fat, or lowcarbohydrate eating plans (26,69,74,75).”

Physical training can play a significant role in the prevention of insulin resistance and type 2 diabetes.

“In addition, physical training can play a significant role in the prevention of insulin resistance and type 2 diabetes [22–25].”

Interventions that focused on physical activity during early pregnancy have been shown to reduce the development of GDM and type 2 diabetes in at-risk individuals.

“Interventions that focussed on physical activity during early pregnancy have been shown to reduce the development of GDM [23, 27] and type 2 diabetes in at risk individuals [16, 56].”

Even moderate (e.g., 10%) weight loss improves all cardiometabolic risk factors simultaneously in obese patients.

“Diet-induced fat loss is recommended for obese patients who have these cardiometabolic risk factors, because even moderate (e.g., 10%) weight loss improves all risk factors simultaneously (1-3).”

Small long-term reductions in body weight (fat) improve glucose tolerance and the other metabolic CHD risk factors evaluated in the present study.

“Small long-term reductions in body weight (fat) improve glucose tolerance and the other metabolic CHD risk factors evaluated in the present study (2,3,12-14).”

The composite outcome, as defined by CDC 2021 standards, comprises elements each associated with reduced risk of progression to diabetes.

“The composite outcome, as defined by the CDC in its 2021 standards,29 comprises elements that have each been associated with reduced risk of progression to diabetes.30-34”

Regular physical activity and behavioral strategies are important components of lifestyle therapy for weight management.

“Regular physical activity, which can contribute to both weight loss and prevention of weight regain, and behavioral strategies are also important components of lifestyle therapy for weight management (26,74,83,135 -137).”

The efficacy of interventions for primary prevention of type 2 diabetes has mainly been demonstrated among individuals who have impaired glucose tolerance (IGT) with or without elevated fasting glucose, not for individuals with isolated impaired fasting glucose (IFG) or for those with prediabetes defined by A1C criteria.

“Moreover, the ef fi cacy of interventions for primary prevention of type 2 diabetes has mainly been demonstrated among individuals who have impaired glucose tolerance (IGT) with or without elevated fasting glucose, not for individuals with isolated impaired fasting glucose (IFG) or for those with prediabetes de fi ned by A1C criteria (5 -8).”

The DPP and other clinical trials have established the feasibility of interrupting the worsening of hyperglycaemia in overweight people with raised fasting or postload glycaemia.

“The DPP and other clinical trials12–16 have established the feasibility of interruption of the worsening of hyperglycaemia in overweight people who have raised fasting or postload glycaemia.”

The Finnish Diabetes Prevention Study demonstrated a 70% reduction in diabetes incidence after adjustment for baseline confounders in individuals who met their physical activity goal but did not meet the accompanying weight loss goal.

“Similar to the DPP trial, the FDPS also demonstrated a 70% reduction in diabetes incidence after adjustment for baseline confounders in individuals who met their PA activity goal (>4 hr-week) but did not meet the accompanying weight loss goal (>5% weight loss) [95] .”

Five clinical trials of reputedly healthy, energy-restricted diets plus increased physical activity in individuals with impaired glucose tolerance showed risk reductions between 30 and 70%.

“Five clinical trials that examined the effects of reputedly healthy, energy-restricted diets together with increased physical activity in individuals with impaired glucose tolerance, a prediabetic stage, showed risk reductions between 30 and 70% ( 2 – 6 ).”

Lifestyle modification reduces the incidence of diabetes among high-risk individuals.

“The results of these studies provide convincing evidence that lifestyle modification reduces the incidence of diabetes among high-risk individuals.”

Regular physical activity by itself or as part of a comprehensive lifestyle plan can prevent progression to type 2 diabetes in high-risk individuals.

“Regular physical activity by itself (155,156) or as part of a comprehensive lifestyle plan (26,74,83,151) can prevent progression to type 2 diabetes in highrisk individuals.”

Lifestyle interventions are proven to effectively prevent type-2 diabetes.

“Lifestyle interventions are proven to effectively prevent type-2 diabetes [16].”

Although interventions can clearly reduce diabetes incidence over a period of a few years, it is not well known how long their effects persist, especially when interventions cease or become less intensive.

“Although interventions can clearly reduce diabetes incidence over a period of a few years,1–5 it is not well known how long their effects persist, especially when interventions cease or become less intensive.”

Several large type 2 diabetes prevention RCTs used low-fat eating plans to achieve weight loss and improve glucose tolerance, and some demonstrated decreased incidence of diabetes.

“Several large type 2 diabetes prevention RCTs (26,74,83,84) used low-fat eating plans to achieve weight loss and improve glucose tolerance, and some demonstrated decreased incidence of diabetes (26,74,83).”

Intensive lifestyle intervention has been shown to prevent or delay the development of type 2 diabetes in other studies.

“Intensive lifestyle intervention has also been shown to prevent or delay the development of type 2 diabetes in other studies.15, 26”

In the Diabetes Prevention Program and the Finnish trials, lifestyle intervention including modest weight loss was effective in preventing the development of diabetes in a high risk population.

“In the Diabetes Prevention Program (DPP) and the Finnish trials, lifestyle intervention including modest weight loss was effective in preventing the development of diabetes in a high risk population [15,16].”

The Da Qing study, the Finnish Diabetes Prevention Study, and the DPP all showed a reduction in risk to develop Type 2 diabetes by up to 58% compared to placebo.

“All three of these large intervention studies showed a reduction in risk to develop Type 2 diabetes by up to 58% compared to placebo.”

There is no published evidence that treatment based on screening has an effect on long-term complications.

“Despite these recommendations and the demonstration that interventions can delay and sometimes prevent the onset of type 2 diabetes in individuals with impaired glucose tolerance (26,27), there is as yet no published evidence that treatment based on screening has an effect on long-term complications.”

Programs combining exercise and modest calorie-restricted weight loss cut diabetes incidence by about 60%.

“Clearly lifestyle interventions, including exercise training and at least mild weight reduction with caloric restriction, showed a nearly 60% reduction in the risk of developing DM, which was considerably better than that noted in patients treated with metformin (73,74).”

Those lifestyle interventions outperform metformin for diabetes risk reduction.

“Clearly lifestyle interventions, including exercise training and at least mild weight reduction with caloric restriction, showed a nearly 60% reduction in the risk of developing DM, which was considerably better than that noted in patients treated with metformin (73,74).”

In youth with type 2 diabetes, both microalbuminuria and retinopathy increase with diabetes duration, and severity is related to glycaemic control.

“Both microalbuminuria and retinopathy increase with diabetes duration and severity is related to glycaemic control163,164.”

Several trials have demonstrated reductions in the risk of developing diabetes among prediabetic individuals after lifestyle and drug-based interventions.

“Several trials have demonstrated reductions in the risk of developing diabetes among prediabetic individuals after lifestyle and drug-based interventions.15,24–28”

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”

The Finnish Diabetes Prevention Study and the US DPP with a 3-year follow-up found a 58% risk reduction after interventions aimed at weight loss, dietary change, and increased physical activity.

“The Finnish Diabetes Prevention Study and, the largest to date, the US DPP with a 3-year follow-up found a 58% risk reduction after interventions aimed at weight loss, dietary change and increase in physical activity.25,28”

The accretion of lean tissue with exercise has a potentially beneficial effect in preventing diabetes and metabolic syndrome, functional dependency, falls, and fractures as well as in the treatment of chronic diseases and disabilities that are often accompanied by disuse, catabolism, and sarcopenia.

“The accretion of lean tissue with exercise has a potentially beneficial effect in preventing diabetes and metabolic syndrome [330], functional dependency, falls, and fractures as well as in the treatment of chronic diseases and disabilities that are often accompanied by disuse, catabolism, and sarcopenia.”

The accretion of lean tissue with exercise has potentially beneficial effects in preventing diabetes, metabolic syndrome, functional dependency, falls, fractures, and treating chronic diseases and disabilities accompanied by disuse, catabolism, and sarcopenia.

“The accretion of lean tissue with exercise has a potentially beneficial effect in preventing diabetes and metabolic syndrome [330], functional dependency, falls, and fractures as well as in the treatment of chronic diseases and disabilities that are often accompanied by disuse, catabolism, and sarcopenia.”

Complex interventions that include dietary changes can prevent progression from impaired glucose tolerance to diabetes.

“There is good evidence that complex interventions, including dietary changes, can prevent the progression of impaired glucose tolerance to diabetes (1,2).”

Earlier identification of individuals at risk for type 2 diabetes is particularly important given effective interventions and the increasing burden of the condition.

“Given the availability of effective interventions for delaying or preventing the onset of type 2 diabetes and the increasing burden of the condition worldwide, earlier identification of individuals at risk is particularly important3-6.”

In metabolic syndrome patients with IFG or IGT, weight reduction, increased physical activity, or both delay or prevent onset of type 2 diabetes mellitus.

“In metabolic syndrome patients with IFG (or IGT if assessed), weight reduction, increased physical activity, or both will delay (or prevent) the onset of type 2 diabetes mellitus.145,174”

Sucrose-rich sweets and juices are thought likely to worsen glycemic control and promote the metabolic syndrome.

“However, they should abstain from sucrose‐rich sweets and juices, which are thought likely to worsen glycemic control and promote the metabolic syndrome 15 , 16 .”

Long-term exercise is shown to reduce risk factors for cardiovascular disease and improve quality of life (QOL) in patients with type 1 diabetes.

“Despite lack of consensus on its role in improving glycemic control in patients with type 1 diabetes, long‐term exercise is shown to reduce risk factors for cardiovascular disease and improve quality of life (QOL) 15 , 16 , 17 , 18 (grade B: 100% agreement).”

DPP-4 inhibitor monotherapy has a small risk of hypoglycemia.

“While the risk of hypoglycemia with DPP‐4 inhibitor monotherapy is small, combination therapy with an SU or insulin often increases the risk of hypoglycemia, suggesting the rationale for reducing the dose of either partnering agent 14 , 15 , 16 , 17 , 18 .”

Combination therapy of a DPP-4 inhibitor with an SU or insulin often increases the risk of hypoglycemia.

“While the risk of hypoglycemia with DPP‐4 inhibitor monotherapy is small, combination therapy with an SU or insulin often increases the risk of hypoglycemia, suggesting the rationale for reducing the dose of either partnering agent 14 , 15 , 16 , 17 , 18 .”

Combination therapy with insulin and oral glucose-lowering agents improves glycemic control and reduces the insulin dose in patients with type 2 diabetes.

“Combination therapy with insulin and oral glucose‐lowering agents (SUs 13 , 14 , fast‐acting insulin secretagogues [glinides] 15 , 16 , 17 ), biguanides 18 , 19 , 20 , 21 , α‐glucosidase inhibitors 22 , 23 , insulin sensitizers 24 , 25 , 26 , 27 , and, DPP‐4 inhibitors 28 , and SGLT2 inhibitors 29 or GLP‐1 receptor agonists 30 are shown to improve glycemic control and reduce the insulin dose being”

Real-time continuous glucose monitoring (rt-CGM) may be more effective than SMBG in improving glycemic control in pediatric and adult patients with type 1 diabetes and in adult patients with type 2 diabetes.

“A number of reports in the literature suggest that real‐time continuous glucose monitoring (rt‐CGM) may be more effective than self‐monitoring of blood glucose (SMBG) in improving glycemic control not only in pediatric and adult patients with type 1 diabetes but in adult patients with type 2 diabetes 13 , 14 , 15 .”

Diabetic retinopathy is a risk factor for diabetic nephropathy and macroangiopathy.

“Diabetic retinopathy is a risk factor for diabetic nephropathy and macroangiopathy 15 , 16 , 17 , 18 , 19 , 20 .”

Anti-dyslipidemic agents (e.g., fibrates, statins) are likely effective in inhibiting the progression of diabetic nephropathy in patients with intact renal function.

“Anti‐dyslipidemic agents (e.g., fibrates, statins) are shown likely to be effective in inhibiting the progression of diabetic nephropathy in patients with intact renal function 14 , 15 , 16 (grade B: 81% agreement).”

Foot ulcer treatment is effective in maintaining the quality of life (QOL) of affected patients.

“Foot ulcer treatment has been shown to be effective in maintaining the QOL of affected patients 14 , 15 (grade A: 100% agreement).”

Lipid control is effective in the primary and secondary prevention of diabetic macroangiopathy.

“Lipid control has been shown to be effective in the primary and secondary prevention of diabetic macroangiopathy 14 , 15 (grade A: 100% agreement).”

Mental/psychological factors significantly affect the patient's diabetes management and prognosis.

“Given that mental/psychological factors have been shown to significantly affect the patient’s diabetes management and prognosis, mental/psychological counseling is to be offered with sufficient care given to addressing individual differences in mental/psychological maturity 14 , 15 .”

Not only aerobic exercise but muscle training is associated with a reduced risk of type 2 diabetes, with their combination markedly decreasing the risk further.

“Not only aerobic exercise but muscle training is associated with a reduced risk of type 2 diabetes, with their combination shown to markedly decrease the risk further 14 , 15 .”

The increased prevalence of insulin resistance in Asian-Indian men may explain the lower efficacy of lifestyle intervention in the Indian diabetes prevention study compared with the U.S. and Finnish diabetes prevention studies.

“which may have important therapeutic implications for prevention and treatment of T2DM in this ethnic group and possibly explain the lower efficacy of lifestyle intervention in the Indian diabetes prevention study compared with the U.S. and Finnish diabetes prevention studies (33-35).”

Randomized controlled clinical trials have shown that weight loss and increased physical activity reduce the incidence of type 2 diabetes in high-risk individuals, including American Indians with IGT.

“Furthermore, randomized controlled clinical trials have shown that weight loss and increased physical activity reduce the incidence of type 2 diabetes in high-risk individuals, including American Indians, who have IGT (27,28).”

In both the Finnish Diabetes Prevention Study and the U.S. Diabetes Prevention Program, lifestyle intervention significantly reduced diabetes incidence by 58%.

“In both the Finnish Diabetes Prevention Study (60) and the U.S. Diabetes Prevention Program (DPP) (61), lifestyle intervention significantly reduced diabetes incidence by 58%.”

Randomized controlled trial evidence of dietary interventions and diabetes prevention only exists for low-fat, low-calorie, plus/minus high-fiber diets.

“However, randomized controlled trial evidence of dietary interventions and diabetes prevention only exists for low-fat, low-calorie, plus/minus high-fiber diets (22,32).”

In the Finnish Diabetes Prevention Program, weight loss counseling targeted to 5% total body weight, decreased total and saturated fat consumption, increased fiber consumption and increased activity to 30 min/day resulted in a 58% reduction in incident T2DM in individuals with IGT and BMI greater than 25 kg/m2.

“In the Finnish Diabetes Prevention Program, weight loss counseling targeted to 5% total body weight, decreased total and saturated fat consumption, increased fiber consumption and increased activity to 30 min/day resulted in a 58% reduction in incident T2DM in individuals with IGT and BMI greater than 25 kg/m2.”

In adults at risk for diabetes, a program of diet and physical activity reduced the risk of diabetes by 58%, with size of the decrease related to the extent of change in lifestyle.

“In adults at risk for diabetes, a program of diet and physical activity reduced the risk of diabetes by 58%, with size of the decrease related to the extent of change in lifestyle.159”

The efficacy of interventions for primary prevention of type 2 diabetes has primarily been demonstrated among individuals with IGT, not individuals with IFG who do not also have IGT.

“The efficacy of interventions for primary prevention of type 2 diabetes (10–16) has primarily been demonstrated among individuals with IGT, not individuals with IFG (who do not also have IGT).”

Metformin, acarbose, orlistat, and thiazolidinediones each have been shown to decrease incident diabetes to various degrees.

“These interventions include intensive lifestyle modification programs that have been shown to be very effective (≥58% reduction after 3 years) and use of the pharmacologic agents metformin, acarbose, orlistat, and thiazolidinediones (TZDs), each of which has been shown to decrease incident diabetes to various degrees.”

Intensive lifestyle modification programs have been shown to be very effective (≥58% reduction after 3 years) in decreasing incident diabetes.

“These interventions include intensive lifestyle modification programs that have been shown to be very effective (≥58% reduction after 3 years) and use of the pharmacologic agents metformin, acarbose, orlistat, and thiazolidinediones (TZDs), each of which has been shown to decrease incident diabetes to various degrees.”

Randomized controlled trials have shown that individuals at high risk for developing diabetes (those with IFG, IGT, or both) can be given interventions that significantly decrease the rate of onset of diabetes.

“Randomized controlled trials have shown that individuals at high risk for developing diabetes (those with IFG, IGT, or both) can be given interventions that significantly decrease the rate of onset of diabetes (10–16).”

Regular exercise may prevent type 2 diabetes in high-risk individuals.

“Furthermore, regular exercise may prevent type 2 diabetes in high-risk individuals (10–12).”