]. The Influence of Age on the Effects of Lifestyle Modification and Metformin in Prevention of Diabetes
Open accessAbstract
BACKGROUND: The incidence of type 2 diabetes increases with age. It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults. METHODS: The Diabetes Prevention Program (DPP) demonstrated that an intensive lifestyle intervention (ILS) or metformin could prevent or delay diabetes. A predefined secondary outcome of DPP was to determine if treatment effects varied by age. RESULTS: At baseline, participants aged 60-85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups. Diabetes incidence rates did not differ by age in the placebo group, but ILS was more effective with increasing age (6.3, 4.9, and 3.3 cases per 100 person-years, in the 25-44, 45-59, and 60-85 year age groups, respectively; p(trend) =.007). Participants aged 60-85 years had the most weight loss and metabolic equivalent (MET)-hours of physical activity. The metformin group showed a trend toward higher diabetes incidence among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in the 25-44, 45-59, and 60-85 year age groups, respectively; p(trend) =.07); and diabetes risk increased with age (hazard ratio [age 60-85 vs 25-44] 1.63, p =.02), after adjusting for the greater weight loss in the 60-85 year age group. CONCLUSIONS: Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity. The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion. A lifestyle modification program can be recommended for older individuals at high risk for type 2 diabetes.
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Written from the paper’s full text.
TL;DR
In the Diabetes Prevention Program, intensive lifestyle intervention (ILS) prevented diabetes more effectively with increasing age, while metformin showed a borderline trend toward reduced effectiveness in older participants. The age-related ILS advantage was largely explained by greater weight loss and physical activity in the 60–85 year group.
Key findings
- Diabetes incidence in the placebo group did not differ by age (11.0, 10.8, and 10.3 cases per 100 person-years in the 25–44, 45–59, and 60–85 year groups; p = .71).
- ILS became more effective with increasing age: 6.3, 4.9, and 3.3 cases per 100 person-years in the 25–44, 45–59, and 60–85 year groups, respectively (p trend = .007). The 60–85 vs 25–44 hazard ratio was 0.47 (95% CI, 0.28–0.78) in Model 1, but the age difference disappeared after adjusting for time-dependent weight, calorie intake, and activity (HR, 0.83; 95% CI, 0.46–1.50).
- Metformin showed a borderline trend toward higher diabetes incidence with age: 6.7, 7.7, and 9.3 cases per 100 person-years in the 25–44, 45–59, and 60–85 year groups (p trend = .07). In Table 4, the 60–85 vs 25–44 hazard ratio was 1.45 (95% CI, 0.98–2.16) in Model 1 and 1.37 (95% CI, 0.87–2.16) in Model 3.
- Older participants had the most weight loss and physical activity: mean weight change was −6.4 kg in the 60–85 group vs −4.1 kg and −5.0 kg in the younger groups; recreational activity change was 18.7 MET-h/wk vs 4.4 and 5.8 MET-h/wk; 55% vs 33% and 39% reached the 7% weight-loss goal, and 48% vs 34% and 38% reached the 150 min/wk exercise goal.
Methods
- This was a predefined secondary analysis of the Diabetes Prevention Program, a multicenter randomized controlled trial. Participants were aged ≥25 years with impaired glucose tolerance and fasting plasma glucose 95–125 mg/dL; they were randomized to ILS, metformin 850 mg twice daily, or placebo, and followed for an average of 3.2 years.
- For this analysis, participants were divided into three age groups: 25–44, 45–59, and 60–85 years. Diabetes was determined by annual oral glucose tolerance testing and semiannual fasting plasma glucose, with confirmation by a second test.
- Analyses used Kruskal-Wallis tests for baseline characteristics, mixed-effects models for continuous changes, generalized estimating equations for goal attainment, and Cox proportional hazards models for time to diabetes, with linear trend tests and step-down Bonferroni adjustment for pairwise comparisons.
Limitations
- The paper states that ethnic and sex distributions were unequal across age groups, with men and Caucasians over-represented among older participants; the study had limited power to detect age differences in this predefined secondary outcome; and the DPP cohort was relatively healthy and motivated, excluding individuals with significant physical limitations, so results may not apply to frail or disabled elderly persons.
- The paper also states that the numbers precluded meaningful stratified analyses to examine the effect of unequal ethnic and sex distributions in some age groups.
- The text makes evident that age-group comparisons are nonrandomized even though treatment assignment was randomized, so residual confounding by age-related factors cannot be excluded.
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Claims the paper makes
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- Findingown data
In the placebo group, there were no significant changes in weight at any age.
“In contrast, there were no significant changes in weight or waist circumference at any age in the placebo group.”
Quote in the paperNot a substantial claim - Findingown data
At baseline, participants aged 60-85 years had the lowest insulin secretion compared to younger age groups.
“At baseline, participants aged 60-85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups.”
- Also stated in: § RESULTS · plain
“The 60-85 year age group also had the lowest baseline waist circumference, weight, body mass index, insulin secretion, and insulin resistance.”
- Also stated in: § DISCUSSION · plain
“The three age groups were generally well matched at baseline for glucose parameters, but the older group was significantly more insulin-sensitive and had greater impairment of insulin secretion than the young or middle-aged groups.”
Quote in the paperNot a substantial claim - Also stated in: § RESULTS · plain
- Findingown data
In the placebo group, there were no significant changes in waist circumference at any age.
“In contrast, there were no significant changes in weight or waist circumference at any age in the placebo group.”
Quote in the paperNot a substantial claim - Findingown data
ILS was effective in all age groups.
“Although ILS was effective in all age groups, diabetes incidence rates fell with increasing age”
Quote in the paperSubstantial claim - Findingown data
In the ILS group, reduction in waist circumference increased with increasing age.
“Weight loss, reduction in waist circumference, and percentage of participants who achieved the 7% weight loss goal all increased with increasing age.”
Quote in the paperNot a substantial claim
- Findingown data
In the ILS group, weight loss increased with increasing age.
“Weight loss, reduction in waist circumference, and percentage of participants who achieved the 7% weight loss goal all increased with increasing age.”
Quote in the paperNot a substantial claim - Findingown data
There were no age differences in reduction of reported caloric intake.
“There were no differences in reduction of reported caloric intake or in the percent reverting to normal glucose tolerance among the age groups.”
Quote in the paperNot a substantial claim - Findingown data
Diabetes incidence rates did not differ by age in the placebo group.
“Diabetes incidence rates did not differ by age in the placebo group, but ILS was more effective with increasing age”
- Also stated in: § RESULTS · plain
“Diabetes incidence did not differ by age in the placebo group (11.0, 10.8, and 10.3 cases per 100 person-years in young, middle-aged, and older groups, respectively; p ¼ .71).”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · plain
- Findingown data
There were no age differences in the percent reverting to normal glucose tolerance.
“There were no differences in reduction of reported caloric intake or in the percent reverting to normal glucose tolerance among the age groups.”
Quote in the paperNot a substantial claim - Findingown data
Older participants were more likely to achieve the exercise goal of 150 min/wk.
“Older participants also reported greater MET-h/wk of recreational activity and were more likely to achieve the exercise goal of 150 min/wk.”
Quote in the paperNot a substantial claim - Findingown data
In the metformin group, diabetes incidence showed a trend toward higher rates among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in 25-44, 45-59, and 60-85 year age groups, respectively; p trend = .07).
“The metformin group showed a trend toward higher diabetes incidence among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in the 25-44, 45-59, and 60-85 year age groups, respectively; p trend ¼ .07)”
- Also stated in: § RESULTS · hedged
“In contrast, diabetes incidence in the metformin group was lowest among the youngest participants (6.7 vs 7.7 vs 9.3 cases per 100 person-years; p trend ¼ .07), a trend that was of borderline significance.”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · hedged
- Findingown data
Older participants reported greater MET-hours per week of recreational activity.
“Older participants also reported greater MET-h/wk of recreational activity and were more likely to achieve the exercise goal of 150 min/wk.”
Quote in the paperNot a substantial claim - Findingown data
In the ILS group, diabetes risk in the 60-85 year age group was approximately half that in the 25-44 year age group (HR 0.47; 95% CI 0.28-0.78).
“For the ILS group, diabetes risk in the 60-85 year age group was approximately one half that in the 25-44 year age group (hazard ratio, 0.47; 95% confidence interval [CI], 0.28-0.78);”
Quote in the paperSubstantial claim - Findingown data
At baseline, participants aged 60-85 years were leaner than younger age groups.
“At baseline, participants aged 60-85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups.”
- Also stated in: § RESULTS · plain
“The 60-85 year age group also had the lowest baseline waist circumference, weight, body mass index, insulin secretion, and insulin resistance.”
Quote in the paperNot a substantial claim - Also stated in: § RESULTS · plain
- Findingown data
ILS was more effective with increasing age, with diabetes incidence rates of 6.3, 4.9, and 3.3 cases per 100 person-years in the 25-44, 45-59, and 60-85 year age groups, respectively (p trend = .007).
“ILS was more effective with increasing age (6.3, 4.9, and 3.3 cases per 100 person-years, in the 25-44, 45-59, and 60-85 year age groups, respectively; p trend ¼ .007).”
- Also stated in: § RESULTS · plain
“Although ILS was effective in all age groups, diabetes incidence rates fell with increasing age (6.3 vs 4.9 vs 3.3 cases per 100 person-years in the 25-44, 45-59, and 60-85 year age groups, respectively; p trend ¼ .007).”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · plain
- Findingown data
At baseline, participants aged 60-85 years had the best insulin sensitivity (lowest insulin resistance) compared to younger age groups.
“At baseline, participants aged 60-85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups.”
- Also stated in: § RESULTS · plain
“The 60-85 year age group also had the lowest baseline waist circumference, weight, body mass index, insulin secretion, and insulin resistance.”
- Also stated in: § DISCUSSION · plain
“The three age groups were generally well matched at baseline for glucose parameters, but the older group was significantly more insulin-sensitive and had greater impairment of insulin secretion than the young or middle-aged groups.”
Quote in the paperNot a substantial claim - Also stated in: § RESULTS · plain
- Findingown data
In the ILS group, the percentage of participants achieving the 7% weight loss goal increased with increasing age.
“Weight loss, reduction in waist circumference, and percentage of participants who achieved the 7% weight loss goal all increased with increasing age.”
Quote in the paperNot a substantial claim - Findingown data
In the ILS group, adjustment for baseline glucose, insulin sensitivity, and insulin secretion produced little change in the age difference (HR 0.50; 95% CI 0.29-0.89).
“and there was little change following adjustment for baseline glucose, insulin sensitivity, and insulin secretion (hazard ratio, 0.50; 95% CI, 0.29-0.89).”
Quote in the paperSubstantial claim - Findingown data
In both the metformin and placebo groups, there was a trend toward increased medication adherence with age.
“In both the metformin and placebo groups, there was a trend toward increased medication adherence and increased recreational activity with age.”
Quote in the paperNot a substantial claim - Findingown data
ILS became significantly more effective than metformin with increasing age (p = .005).
“ILS became significantly more effective than metformin with increasing age ( p ¼ .005).”
Quote in the paperSubstantial claim - Findingown data
The strength of the association between age and declining metformin effect was attenuated when small differences in baseline fasting glucose values were included in the model.
“Although baseline glucose variables were almost identical in the three age groups, the strength of the association between age and declining metformin effect was attenuated when the small differences in baseline fasting glucose values (106 vs 107 mg/dL, in the 25-44 and 60-85 year age groups, respectively) were included in the model.”
Quote in the paperSubstantial claim - Findingown data
In the metformin group, the trend toward greater diabetes risk in the 60-85 year age group was attenuated following adjustment for baseline metabolic parameters (HR 1.26; 95% CI 0.80-1.93).
“This trend was attenuated following adjustment for baseline metabolic parameters (hazard ratio, 1.26; 95% CI, 0.80-1.93)”
Quote in the paperNot a substantial claim - Findingown data
Younger participants were more likely to live in households with four or more members (50% vs 29% vs 12%).
“As expected, younger participants were more likely to be employed (85% vs 82% vs 39%) and to live in households with four or more members (50% vs 29% vs 12%).”
Quote in the paperNot a substantial claim - Findingown data
The three age groups were generally well matched at baseline for glucose parameters.
“The three age groups were generally well matched at baseline for glucose parameters, but the older group was significantly more insulin-sensitive and had greater impairment of insulin secretion than the young or middle-aged groups.”
Quote in the paperNot a substantial claim - Findingown data
In the ILS group, after adjusting for time-dependent change in weight, calorie intake, and activity, the age difference in diabetes risk disappeared (HR 0.83; 95% CI 0.46-1.50).
“After adjusting for time-dependent change in weight, calorie intake, and activity, the age difference disappeared (hazard ratio, 0.83; 95% CI, 0.46-1.50).”
Quote in the paperSubstantial claim - Findingown data
Younger participants were more likely to be employed (85% vs 82% vs 39%).
“As expected, younger participants were more likely to be employed (85% vs 82% vs 39%) and to live in households with four or more members (50% vs 29% vs 12%).”
Quote in the paperNot a substantial claim - Findingown data
The pattern of higher diabetes hazard ratio with high insulin sensitivity and low insulin secretion was not observed in the placebo or lifestyle groups.
“However, this pattern was not observed in the placebo or lifestyle groups, suggesting that metformin effectiveness is tied to metabolic profile, being most effective in insulin-resistant individuals and less so in those individuals whose predominant metabolic defect is impaired insulin secretion.”
Quote in the paperSubstantial claim - Findingown data
Among participants who developed diabetes, the youngest group was more likely to convert by fasting criteria (62% vs 53% vs 45%).
“among those participants who developed diabetes during the DPP, the youngest group was more likely to convert by fasting criteria (62% vs 53% vs 45%), and the oldest group by 2-hour criteria (38% vs 47% vs 55%; p , .01), an observation consistent with previous reports (22).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
- Findingown data
Among participants who developed diabetes, the oldest group was more likely to convert by 2-hour criteria (38% vs 47% vs 55%; p < .01).
“among those participants who developed diabetes during the DPP, the youngest group was more likely to convert by fasting criteria (62% vs 53% vs 45%), and the oldest group by 2-hour criteria (38% vs 47% vs 55%; p , .01), an observation consistent with previous reports (22).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
- Findingown data
Baseline glucose variables were almost identical in the three age groups.
“Although baseline glucose variables were almost identical in the three age groups, the strength of the association between age and declining metformin effect was attenuated when the small differences in baseline fasting glucose values (106 vs 107 mg/dL, in the 25-44 and 60-85 year age groups, respectively) were included in the model.”
- Also stated in: § RESULTS · plain
“Baseline fasting plasma glucose and 2-hour glucose were similar in all 3 age groups.”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · plain
- Findingown data
Baseline fasting plasma glucose and 2-hour glucose were similar in all 3 age groups.
“Baseline fasting plasma glucose and 2-hour glucose were similar in all 3 age groups.”
Quote in the paperNot a substantial claim - Findingown data
The pattern of younger participants converting by fasting glucose and older by 2-hour criteria was most apparent in the metformin group.
“This pattern was most apparent in the metformin group”
Quote in the paperSubstantial claim - Findingown data
Diabetes risk reduction did not differ by ethnic group.
“diabetes risk reduction did not differ by ethnic group.”
Quote in the paperSubstantial claim - Findingown data
In the metformin group, older participants (60-85) lost more weight than younger participants (25-44).
“Metformin | Weight change, kg | À1.5 (0.3) | À1.7 (0.2) | À2.7 (0.3) | .001* ,y”
Quote in the paperNot a substantial claim - Findingown data
In the lifestyle group, older participants (60-85) lost more weight than younger participants (25-44 and 45-59).
“Weight change, kg | À4.1 (0.4) À5.0 (0.3) À6.4 (0.3) ,.001 #, * ,y”
Quote in the paperNot a substantial claim - Findingown data
Diabetes risk reduction did not differ significantly between male and female ILS participants (62% vs 52%, p=.25).
“although diabetes risk reduction did not differ significantly (62% for men vs 52% for women; p ¼ .25).”
Quote in the paperNot a substantial claim - Premisecitation
Lifestyle modification reduced the development of diabetes by 55% in the DPP cohort as a whole.
“Metformin reduced the development of diabetes by 30%, and lifestyle modification did so by 55% in the cohort as a whole (1,9).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [1] source
Not checked in the free run.
- cites [9]
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- Premisecitation
Within the metformin group, participants with the highest insulin sensitivity and lowest insulin secretion had a greater hazard ratio for diabetes than did those with the lowest insulin sensitivity and greatest insulin secretion.
“Within the metformin group, those participants with the highest insulin sensitivity and lowest insulin secretion (the pattern typical of older adults) had a greater hazard ratio for diabetes than did those participants with the lowest insulin sensitivity and greatest insulin secretion (typical of younger adults) (9).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9]
Not checked in the free run.
- Interpretationown data
The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion.
“The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion.”
Quote in the paperSubstantial claim - Interpretationreasoning
One explanation for these results is a survivor effect: persons who survived to a later age without developing diabetes tended to be somewhat leaner and less insulin resistant than age-mates who did become diabetic.
“One explanation for these results is a ''survivor effect''-that is, those persons who survived to a later age without developing diabetes tended to be somewhat leaner and less insu-lin resistant than were age-mates who did become diabetic.”
Quote in the paperSubstantial claim - Premisecitation
Metformin reduced the development of diabetes by 30% in the DPP cohort as a whole.
“Metformin reduced the development of diabetes by 30%, and lifestyle modification did so by 55% in the cohort as a whole (1,9).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [1] source
Not checked in the free run.
- cites [9]
Not checked in the free run.
- Interpretationown data
The pattern of decreased metformin effect with age suggests that there may be true differences in physiology and pharmacologic response.
“Nonetheless, the pattern of decreased metformin effect with age suggests that there may be true differences in physiology and pharmacologic response.”
Quote in the paperSubstantial claim - Interpretationown data
Other biological factors in the greater ILS effectiveness in older adults are suggested by their better baseline body size and glycemic profile and the stronger effect on postchallenge glycemia.
“These results appear to be due to more active participation in ILS activities by the older group, although other (biological) factors are suggested by their better baseline body size and glycemic profile and the stronger effect on postchallenge glycemia.”
Quote in the paperSubstantial claim - Interpretationown data
The greater effectiveness of lifestyle modification in older individuals was largely explained by greater weight loss and physical activity.
“Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity.”
Quote in the paperSubstantial claim - Interpretationown data
The greater effectiveness of ILS in older adults appears to be due to more active participation in ILS activities by the older group.
“These results appear to be due to more active participation in ILS activities by the older group, although other (biological) factors are suggested by their better baseline body size and glycemic profile and the stronger effect on postchallenge glycemia.”
Quote in the paperSubstantial claim - Interpretationown data
The effectiveness of a comprehensive ILS program in preventing deterioration of glucose tolerance is enhanced in older adults.
“However, our data suggest that the effectiveness of a comprehensive ILS program in preventing deterioration of glucose tolerance is enhanced in older adults.”
Quote in the paperSubstantial claim - Premisecitation
The DPP demonstrated that an intensive lifestyle intervention or metformin could prevent or delay diabetes.
“The Diabetes Prevention Program (DPP) demonstrated that an intensive lifestyle intervention (ILS) or metformin could prevent or delay diabetes.”
- Also stated in: § Abstract · boosted
“The Diabetes Prevention Program (DPP), a multicenter, randomized, controlled trial, demonstrated that medication (metformin) or lifestyle modification could prevent or delay the development of diabetes in a high-risk population who had IGT and an elevated fasting glucose.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [1] source
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- cites [9]
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- Also stated in: § Abstract · boosted
- Interpretationown data
Lifestyle modification was exceptionally effective in preventing diabetes in older individuals.
“Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity.”
Quote in the paperSubstantial claim - Premisecitation
Baseline insulin sensitivity and secretion were strong and independent predictors of diabetes risk in the DPP.
“As reported previously (9), baseline insulin sensitivity and secretion were strong and independent predictors of diabetes risk in the DPP.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9]
Not checked in the free run.
- Premisecitation
The effect of aerobic (endurance) training on insulin sensitivity in the elderly population is uncertain, with some reporting a clear benefit and others no effect.
“In contrast, the effect of aerobic (endurance) training on insulin sensitivity in the elderly population is uncertain, with some reporting a clear benefit (36,37) and others no effect, despite increased muscle GLUT4 and mitochondrial oxidative capacity (38).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [36] source
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- cites [37]
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- cites [38]
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- Interpretationown data
The DPP provides unique information about prevention in older adults.
“Other studies have also demonstrated that diabetes can be prevented (or delayed) by lifestyle change (23,24) and medication (25,26), but the DPP provides unique information about prevention in older adults.”
Quote in the paperSubstantial claim - Premisecitation
Several studies in older patients with type 2 diabetes suggested that resistance training can improve glycemic control and insulin sensitivity, independent of weight loss.
“Several studies in older patients with type 2 diabetes suggested that resistance training can improve glycemic control and insulin sensitivity, independent of weight loss (32)(33)(34).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites (32)(33)(34)
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- Premisecitation
In the Baltimore Longitudinal Study of Aging, older adults (>65 years) had substantially accelerated rates of progression to abnormal 2-hour glucose compared to younger persons.
“In that study, older adults (>65 years) had substantially accelerated rates of progression to abnormal 2-hour glucose compared to younger persons.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
- Interpretationreasoning
These results may not apply to frail or disabled elderly persons.
“so these results may not apply to frail or disabled elderly persons.”
Quote in the paperNot a substantial claim- Rests on an assumption: The DPP cohort was a relatively healthy and motivated group.
- Study design and conductown data
The study had limited power to detect age differences in response to intervention.
“the study had limited power to detect these differences”
Quote in the paperSubstantial claim - Interpretationreasoning
The limited effectiveness of metformin may reflect true age-related differences in glucose metabolism and glycemic patterns at diabetes conversion.
“The limited effectiveness of metformin, in contrast, may reflect true age-related differences in glucose metabolism and glycemic patterns at diabetes conversion.”
Quote in the paperSubstantial claim - Interpretationreasoning
Results of DPP demonstrate that an intensive lifestyle modification program is exceptionally effective in preventing diabetes in older individuals with IGT.
“In conclusion, results of the DPP demonstrate that an intensive lifestyle modification program is exceptionally effective in preventing diabetes in older individuals with IGT.”
Quote in the paperSubstantial claim - Interpretationreasoning
The pattern of younger converting by fasting and older by 2-hour criteria is consistent with the relative ineffectiveness of metformin in reducing postchallenge hyperglycemia.
“This pattern was most apparent in the metformin group, and is consistent with the relative ineffectiveness of this agent in reducing postchallenge hyperglycemia.”
Quote in the paperSubstantial claim - Premisecitation
In the Rancho Bernardo Study, isolated postchallenge hyperglycemia was much more common than fasting hyperglycemia as a diagnostic criterion for diabetes.
“In the Rancho Bernardo Study, isolated postchallenge hyperglycemia was much more common than fasting hyperglycemia as a diagnostic criterion for diabetes (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] source
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- Premisecitation
Data from the Baltimore Longitudinal Study of Aging suggest two distinct phenotypes for development of diabetes: one through increased fasting glucose, the other through elevated 2-hour glucose.
“Data from the Baltimore Longitudinal Study of Aging suggest that there may be two distinct phenotypes for the development of diabetes-one through increased fasting glucose and the other through elevated 2-hour glucose levels (22).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
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- Interpretationown data
The robust response to lifestyle intervention in older participants is in large part due to greater weight loss and more active participation in ILS activities among the older participants.
“This robust response is in large part due to greater weight loss and more active participation in ILS activities among the older participants.”
Quote in the paperSubstantial claim - Interpretationreasoning
The observed age differences in treatment effects are unlikely to be explained solely by variations in sex and ethnic composition of the age groups.
“suggesting that the observed age differences in treatment effects are unlikely to be explained solely by variations in sex and ethnic composition of the age groups.”
Quote in the paperSubstantial claim - Interpretationown data
Limited power may have been a factor in the borderline statistical significance of some findings.
“and this may have been a factor in the borderline statistical significance of some of our findings.”
Quote in the paperSubstantial claim - Interpretationreasoning
The DPP ILS program has broad potential applicability for community-dwelling seniors.
“has broad potential applicability for community-dwelling seniors.”
Quote in the paperSubstantial claim- Rests on an assumption: The DPP ILS program was well-tolerated by older participants.
- Study design and conductown data
The numbers preclude meaningful stratified analyses to examine the effect of unequal ethnic and sex distributions in some age groups.
“The numbers also preclude meaningful stratified analyses to examine the effect of unequal ethnic and sex distributions in some age groups.”
Quote in the paperSubstantial claim - Interpretationreasoning
Reduced metformin effectiveness in preventing diabetes in the elderly may be due to the interaction of a specific metabolic profile (insulin secretory defect, leading to postchallenge hyperglycemia) with the drug's pharmacologic action.
“We propose that reduced metformin effectiveness in preventing diabetes in the elderly population may be due to the interaction of a specific metabolic profile (insulin secretory defect, leading to postchallenge hyperglycemia) with the drug's pharmacologic action.”
Quote in the paperSubstantial claim
- May combine two claims. 22
- Classified as probably not a substantial claim. 26
May combine two claims.
Findingown dataIn the metformin group, waist circumference was reduced, with the greatest change in the 60-85 year age group.
“Likewise, waist circumference was reduced, with the greatest change in the 60-85 year age group.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn both the metformin and placebo groups, there was a trend toward increased recreational activity with age.
“In both the metformin and placebo groups, there was a trend toward increased medication adherence and increased recreational activity with age.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationIn the metformin group, participants experienced modest weight loss, which was greatest in the oldest age group.
“As has been previously observed with this drug (21), the metformin participants experienced modest weight loss, which was greatest in the oldest age group.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
May combine two claims.
Findingown dataThe pattern of diabetes conversion was most apparent in the metformin group, although differences by treatment group were not statistically significant.
“This pattern of diabetes conversion was most apparent in the metformin group, although differences by treatment group were not statistically significant.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe mean ages of the young and middle-aged groups were 38.8 and 51.6 years, respectively.
“The mean ages of the young and middle-aged groups were 38.8 and 51.6 years, respectively.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingnone givenMost DPP ILS participants achieved their exercise goal through low-level aerobic activity, such as brisk walking or cycling, with a small contribution from resistance training.
“Most DPP ILS participants achieved their exercise goal through low-level aerobic activity, such as brisk walking or cycling, with a small contribution from resistance training.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataCompared to young and middle-aged participants, older participants were more likely to be male (21% vs 31% vs 49%, p < .0001).
“Compared to young and middle-aged participants, older participants were more likely to be male (21% vs 31% vs 49%, p , .0001) and Caucasian (47% vs 55% vs 66%, p , .0001).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataTwenty percent of participants were 60 years old or older at the beginning of the study, with a mean age of 66.4 years.
“Twenty percent of participants were 60 years old or older at the beginning of the study, with a mean age of 66.4 years.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataCompared to young and middle-aged participants, older participants were more likely to be Caucasian (47% vs 55% vs 66%, p < .0001).
“Compared to young and middle-aged participants, older participants were more likely to be male (21% vs 31% vs 49%, p , .0001) and Caucasian (47% vs 55% vs 66%, p , .0001).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMale ILS participants lost more weight and reported more exercise than female ILS participants.
“Male ILS participants lost more weight and reported more exercise than did female ILS participants”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the lifestyle group, the hazard ratio for diabetes for ages 60-85 vs 25-44 was 0.47 (95% CI 0.28-0.78) in Model 1, 0.50 (0.29-0.89) in Model 2, and 0.83 (0.46-1.50) in Model 3.
“Lifestyle | 60-85 vs 25-44 | 0.47 (0.28-0.78) | ,.01 | 0.50 (0.29-0.89) | .02 | 0.83 (0.46-1.50) | .54”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn the placebo group, older participants had greater increases in recreational activity than younger participants.
“Recreational activity change (MET-h/wk) | À0.9 (1.5) | 3.7 (1.4) | 12.8 (2.5) | ,.001 #, * ,y”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the metformin group, the hazard ratio for diabetes for ages 60-85 vs 25-44 was 1.45 (0.98-2.16) in Model 1, 1.26 (0.80-1.93) in Model 2, and 1.37 (0.87-2.16) in Model 3.
“Metformin | 60-85 vs 25-44 | 1.45 (0.98-2.16) | .06 | 1.26 (0.80-1.93) | .33 | 1.37 (0.87-2.16) | .17”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn the metformin group, older participants had greater increases in recreational activity than younger participants.
“Recreational activity change (MET-h/wk) | À3.0 (1.7) | À1.1 (1.2) | 15.6 (2.1) | ,.001* ,y”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingnone givenCaucasians and Hispanics lost more weight than African Americans did.
“although Caucasians and Hispanics lost more weight than African Americans did”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong metformin participants, diabetes risk reduction was similar in men and women (37% and 27%; p=.41) and among ethnic groups.
“Among metformin participants, diabetes risk reduction was similar in men and women (37% and 27%; p ¼ .41)and among ethnic groups”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAmong DPP participants who progressed to diabetes, younger participants were more likely to convert by fasting glucose criteria, and older participants by 2-hour criteria.
“Among those persons who progressed to diabetes within DPP, we observed that younger participants were more likely to convert by fasting glucose criteria, and older participants by 2-hour criteria.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductcitationDevelopment of diabetes was determined by an annual oral glucose tolerance test and semiannual fasting plasma glucose tests, and required confirmation by a second test, using ADA and WHO criteria.
“Development of diabetes was determined by an annual oral glucose tolerance test and semiannual fasting plasma glucose tests, and required confirmation by a second test, using the criteria of the American Diabetes Association and the World Health Organization (12,13).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [12] source
Not checked in the free run.
- cites [13]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenILS goals and procedures were uniform across all age groups.
“ILS goals and procedures were uniform across all age groups.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningThe prevention or delay of diabetes by metformin or lifestyle modification was the primary outcome in DPP, but a predefined secondary outcome was to determine whether treatment effects varied by age, sex, or race.
“The prevention or delay of diabetes by metformin or lifestyle modification was the primary outcome in DPP, but a predefined secondary outcome was to determine whether treatment effects varied by age, sex, or race.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe older metformin group may have had a somewhat higher risk of diabetes at baseline, which could account for some of the observed difference in treatment effect.
“This finding suggests that the older metformin group may have had a somewhat higher risk of diabetes at baseline, which could account for some of the observed difference in treatment effect.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenAll participants provided written informed consent and signed documents approved by the Institutional Review Board at each center.
“All participants provided written informed consent and signed documents approved by the Institutional Review Board at each center.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataDPP data indicate that there are significant age differences in response to either lifestyle modification or metformin, which appear to reflect variation in both behavior and biology.
“DPP data indicate that there are significant age differences in response to either lifestyle modification or metformin, which appear to reflect variation in both behavior and biology.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenRecruitment into the DPP was designed to represent varied ethnic and racial groups, both sexes, and both younger and older individuals to reflect the U.S. population at risk for diabetes.
“Recruitment into the DPP was designed to represent varied ethnic and racial groups, both sexes, and both younger and older individuals to reflect the U.S. population at risk for diabetes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe reasons for differences in ILS participation among the age groups were not formally assessed in DPP.
“The reasons for differences in ILS participation among the age groups were not formally assessed in DPP.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationown dataThese data support that younger participants had family and work responsibilities that could interfere with lifestyle changes, whereas older participants had fewer competing obligations and more time to devote to the ILS program.
“These data would support anecdotal evidence that younger participants had family and work responsibilities that could interfere with lifestyle changes, whereas older participants had fewer competing obligations and more time to devote to the ILS program.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataMetformin effectiveness is tied to metabolic profile, being most effective in insulin-resistant individuals and less so in those individuals whose predominant metabolic defect is impaired insulin secretion.
“However, this pattern was not observed in the placebo or lifestyle groups, suggesting that metformin effectiveness is tied to metabolic profile, being most effective in insulin-resistant individuals and less so in those individuals whose predominant metabolic defect is impaired insulin secretion.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataTo correct for some imbalance among the three age groups at baseline, the models were adjusted for baseline values when applicable.
“To correct for some imbalance among the three age groups at baseline, the above models were adjusted for baseline values when applicable.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOther studies have demonstrated that diabetes can be prevented or delayed by lifestyle change and medication.
“Other studies have also demonstrated that diabetes can be prevented (or delayed) by lifestyle change (23,24) and medication (25,26), but the DPP provides unique information about prevention in older adults.”
Quote in the paperNot a substantial claim0 of 4 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationValues of p for pair-wise comparison between any two age groups were adjusted for multiple comparisons by using the step-down Bonferroni method.
“Values of p for pair-wise comparison between any two age groups were adjusted for multiple comparisons by using the step-down Bonferroni method (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenTime-dependent proportional hazards analyses were performed to adjust for weight change and physical activity change during the study.
“Timedependent proportional hazards analyses were performed to adjust for weight change and physical activity change during the study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationPhysical activity was assessed using two standardized and validated questionnaires, LoPAR and MAQ, completed annually.
“The amount of physical activity was assessed using two standardized and validated questionnaires, the Low-level Physical Activity Recall (LoPAR) and the Modified Activity Questionnaire (MAQ), which were completed annually (14).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenMedication adherence was determined by pill count at each quarterly visit.
“Medication adherence was determined by pill count at each quarterly visit.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationImprovements in insulin action and reduction in hyperinsulinemia have been reported in older, nondiabetic men following short-term strength training.
“Improvements in insulin action and reduction in hyperinsulinemia have also been reported in older, nondiabetic men following shortterm strength training (35).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] source
Not checked in the free run.
May combine two claims.
PremisecitationAge-related deterioration in glucose tolerance reflects both impaired insulin secretion and declining insulin sensitivity.
“Age-related deterioration in glucose tolerance reflects both impaired insulin secretion and declining insulin sensitivity (27)(28)(29).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites (27)(28)(29)
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe DPP ILS program was not designed to determine the individual effectiveness of diet change versus exercise or to determine the most effective form of exercise.
“The DPP ILS program was not designed to determine the individual effectiveness of diet change versus exercise or to determine the most effective form of exercise.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMetformin's primary mechanism is suppression of hepatic glucose production, which is the major determinant of fasting plasma glucose but plays a minor role in postchallenge hyperglycemia.
“The primary mechanism for the antidiabetic effect of metformin is through suppression of hepatic glucose production, which is the major determinant of fasting plasma glucose levels but plays a more minor role in postchallenge (or postprandial) hyperglycemia (21).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationDietary intake was assessed at baseline and year 1 using a modified version of the Block Food Frequency Questionnaire.
“Dietary intake was assessed at baseline and year 1 by using a modified version of the Block Food Frequency Questionnaire (15).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] source
Not checked in the free run.
May combine two claims.
PremisecitationDiet-induced weight loss improves insulin sensitivity and insulin secretion in older patients.
“Diet-induced weight loss improves insulin sensitivity and insulin secretion in older patients (30), but data are conflicting about whether exercise can enhance insulin action and improve glucose tolerance, independent of weight loss (31).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAge differences in response to intervention was a predetermined secondary outcome in DPP.
“Although age differences in response to intervention was a predetermined secondary outcome in DPP”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductnone givenEthnic and sex distributions were not equal in all age groups, with men and Caucasians over-represented among older participants.
“Ethnic and sex distributions were not equal in all age groups, with men and Caucasians over-represented among older participants.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults.
“It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults.”
The paper relies on this without support.
The incidence of type 2 diabetes increases with age.
“The incidence of type 2 diabetes increases with age.”
The paper relies on this without support.
The metabolic defects underlying the development of diabetes and the ability to adhere to lifestyle modification may vary by age and could influence the effectiveness of diabetes prevention in older individuals.
“The metabolic defects underlying the development of diabetes and the ability to adhere to lifestyle modification may vary by age and could influence the effectiveness of diabetes prevention in older individuals.”
The paper relies on this without support.
The DPP cohort was a relatively healthy and motivated group.
“As noted, the DPP cohort was a relatively healthy and motivated group”
The paper relies on this without support.
The DPP ILS program was well-tolerated by older participants.
“On the whole, the DPP ILS program of low-intensity aerobic activity and low-fat, reduced-calorie diet was well-tolerated by older participants”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The use of metformin may negate some of the positive effects of exercise and lifestyle and have less favorable effects in older subjects.
“the use of metformin may negate some of the positive effects of exercise and lifestyle and less favorable effects in older subjects as was also emphasized by the Diabetes Prevention Program (265, 266).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [265]
In the DPP, older participants seemed to have more efficacy from the lifestyle intervention than younger participants, but did not appear to benefit from metformin.
“These participants seemed to have more efficacy from the lifestyle intervention than younger participants, but did not appear to benefit from metformin13, 18.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Middle age group has conflicting lower bounds
MinorThe Data Analysis section defines the middle age group as 44-59 years, overlapping the 25-44 group at age 44. The tables instead define it as 45-59 years.
“For these analyses, participants were divided into 3 age groups: 25-44 years, 44-59 years, and 60-85 years, representing young, middle-aged, and older age individuals.”
“| Treatment Group | Measures | 25-44 Years | 45-59 Years | 60-85 Years | p Value* |”
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- Authors
- The Diabetes Prevention Program Research Group [Prepared by Jill Crandall, D. S.
- Corresponding author
- The Diabetes Prevention Program Research Group [Prepared by Jill Crandall, David Schade, Yong Ma, Wilfred Y. Fujimoto, Elizabeth Barrett-Connor, Sarah Fowler, Sam Dagogo-Jack, Reubin Andres
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-10-01
- Volume
- 61
- Issue
- 10
- Pages
- 1075-1081
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC1783677
- OpenAlex
- W1508260332
- Semantic Scholar
- 2c6e5b4bb6f1081ba76996200c867a5a41120710
- Cited by
- 254
- References
- 46
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 14 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 15 · 2017: 13 · 2016: 15 · 2015: 16 · 2014: 14 · 2013: 15 · 2012: 26
- FWCI
- 10.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Bristol-Myers Squibb
- George Washington University
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048400, U01DK048411, U01DK048489)
- National Institute of Child Health and Human Development
- National Center for Research Resources
- Office of Women's Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes prevention, age differences, intensive lifestyle intervention, metformin, Diabetes Prevention Program, older adults, weight loss, physical activity, insulin sensitivity, insulin secretion, diabetes incidence
- MeSH terms
- Adult, Age Factors, Aged, Diabetes Mellitus, Type 2, Female, Glucose, Humans, Hypoglycemic Agents, Life Style, Male, Metformin, Middle Aged, Incidence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
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