Prevention of type 2 diabetes through prediabetes remission without weight loss

Obesity is associated with an increased risk of type 2 diabetes (T2D). Pancreatic beta-cell failure is an early event in the development of glucose dysregulation and diabetes. Interventions to halt beta-cell failure in T2D include diet modification, exercise, and use of pharmacologic agents. There is evidence that abdominal obesity may contribute to diabetes through insulin resistance and beta-cell impairment. Pivotal long-term studies into the prevention of T2D have shown the importance of weight loss beside diet, lifestyle, and medication. The Finnish Diabetes Prevention Program (DPP) showed that weight loss gradually reduces the risk of diabetes, and that even modest weight loss can significantly reduce the incidence of T2D. Similarly, in the US DPP, weight loss as part of intensive lifestyle modification was the major factor in reducing the incidence of T2D in high-risk subjects, being more effective than drug intervention. While understanding the relationship between obesity and diabetes is complex, we know that weight loss has positive effects on adipose tissue. It causes an increase in the beneficial fat cell hormone adiponectin, and a decrease in adipose tissue inflammation. Also, it is associated with reduced insulin resistance and a consequential reduction in glucolipotoxicity, which can improve beta-cell function. In summary, weight loss improves glycemic control and thereby mitigates diabetes symptoms and complications, possibly through the preservation of beta-cell function. Therefore, efforts to prevent diabetes and preserve beta-cell function in patients with T2D should more consequently emphasize and target weight loss.

Exercise Versus Pharmacological Interventions for Reducing Visceral Adiposity and Improving Health Outcomes

The Health Risks of Obesity Have Been Exaggerated.

Prevention of type 2 diabetes through lifestyle modification: is there a role for higher-protein diets?

See article in J. Gastroenterol. Hepatol. 2010; 25: 1687–1691.

The Diabetes Prevention Program (DPP) showed that intensive lifestyle intervention reduced the risk of diabetes by 58%. This paper examines demographic, psychosocial, and behavioral factors related to achieving weight loss and physical activity goals in the DPP lifestyle participants. Lifestyle participants (n = 1079; mean age = 50.6, BMI = 33.9, 68% female, and 46% from minority groups) had goals of 7% weight loss and 150 min/wk of physical activity. Goal achievement was assessed at the end of the 16-session core curriculum (approximately week 24) and the final intervention visit (mean = 3.2 years) as a function of demographic, psychosocial, and behavioral variables. Forty-nine percent met the weight loss goal and 74% met the activity goal initially, while 37% and 67%, respectively, met these goals long-term. Men and those with lower initial BMI were more likely to meet activity but not weight loss goals. Hispanic, Asian, and Native Americans were more likely to meet the long-term activity goals, and whites were more likely to meet the initial weight loss goal. In multivariate analyses, meeting the long-term weight loss goal and both activity goals increased with age, while psychosocial and depression measures were unrelated to goal achievement. Dietary self-monitoring was positively related to meeting both weight loss and activity goals, and meeting the activity goal was positively related to meeting the weight loss goal. Participants who met initial goals were 1.5 to 3.0 times more likely to meet these goals long-term. Success at meeting the weight loss and activity goals increased with age. Initial success predicted long-term success. Self-monitoring and meeting activity goals were related to achieving and sustaining weight loss.

Night-time sleep duration and the incidence of obesity and type 2 diabetes. Findings from the prospective Pizarra study

The DPP lifestyle intervention showed that meeting weight loss (WL) and activity goals can prevent/delay T2D. The success of community translated versions of it (e.g., Group Lifestyle Balance, DPP-GLB) has led to Medicare reimbursement based on session attendance (at 6 and 12 months) and participant success at meeting a 5% WL goal at 12 months. Although attendance has been suggested to be related to WL success, the impact of the 6 monthly maintenance sessions (mos 7-12) after the more frequent 16 core sessions (mos 0-6) on one-year WL is not known. This effort examines how maintenance session attendance and WL goal status at 6 months in DPP-GLB affects achievement of the 12-month 5% WL goal. Data were combined from two identical intervention trials that delivered the 12-month DPP-GLB in a community setting to overweight/obese adults (mean age 62 years, 76% women) with prediabetes and/or metabolic syndrome. Participants who attended ≥4 core sessions during the first 6 months and had complete data on maintenance attendance and WL were included (n=238). Meeting the 6-month WL goal was associated with greater odds of meeting the 12-month WL goal (p<.0001). Odds of meeting the 12-month 5% WL goal were significantly greater for those who attended ≥4 maintenance sessions vs. those who did not (OR=6.0, 95% CI: 2.4-15.0). When stratified by achieving the 5% WL goal at 6 months, those who attended ≥4 maintenance sessions and met the 6-month WL goal were more likely to meet the WL goal at 12 months (OR=11.4, CI: 3.2- 40.7) compared to those who failed to meet the WL goal at 6 months (OR=1.5, CI: 0.3-7.5). Adjustment for age, gender and 6-month physical activity yielded similar results. Attending DPP-GLB maintenance sessions and meeting the 6-month WL goal increased the odds of meeting ≥5% WL at 12 months. For those who failed to meet the 6-month WL goal, attending maintenance sessions did not significantly improve their chance of 12-month WL success. Disclosure J. Napoleone: None. R.G. Miller: None. S. Devaraj: None. B. Rockette-Wagner: None. V.C. Arena: None. E.M. Venditti: None. K. Kramer: None. A. Kriska: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R18DK100933, R18DK081323)

The Diabetes Prevention Program (DPP) lifestyle intervention demonstrated that meeting the weight loss (WL) and activity goals prevents/delays type 2 diabetes. Older DPP participants, 60-85 years, reduced the risk of developing diabetes by 71% versus 58% in those <60 years. Currently, community translated DPP-based lifestyle interventions including Group Lifestyle Balance (DPP-GLB), are reimbursed by Medicare for overweight/obese older adults with prediabetes. This effort examined the impact of age group (60-65: reference, 66-70, ≥71 years) on both DPP-GLB maintenance session attendance (months 7-12) and achieving the 5% WL goals at 6- and 12-months. Data were combined from two identical 12-month DPP-GLB intervention trials involving overweight/obese adults with prediabetes and/or metabolic syndrome. Participants ≥60 years attending ≥4 sessions (months 0-6), with complete data on session attendance and WL were included (n=145; age=68.7 + 5.8 years, range 60-88; 79% women). Participants aged 66-70 years (N=46) were more likely to meet the 6-month 5% WL goal (67.4%) vs. 60-65 years (N=51; 45.1%; p=0.03). Participants aged 66-70 (69.6%) and ≥71 years (N=48; 60.4%) were more likely to meet the 12-month WL goal vs. 60-65 years (35.3%; 66-70: p=0.0007; ≥71: p=0.01). Maintenance attendance did not vary by age group with approximately 30% of each group attending ≥4 of 6 maintenance sessions (p=0.55). In conclusion, adults 66+ vs. 60-65 years more successfully met the clinically meaningful 5% WL goals at 6 and 12 months. With nationwide implementation of community-based “real-world” DPP-GLB lifestyle interventions, better understanding of program success across older adult age groups will enhance program reach and effectiveness.

BackgroundPrevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors.MethodsWe analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm−2) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA1c.ResultsMean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P<0.001). Participants with ≥5% weight loss at one year had 65% lower T2D incidence (HR 0.35 (95% CI 0.22 to 0.56) P<0.001); maintaining ≥5% weight loss for two and three years further reduced T2D incidence. Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study (EDIPS) participants with similar hazard-ratios for intervention effect.ConclusionsPooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention. Analysis showed the preventive effect of ≥5% weight loss, especially if maintained long term, which has utility for intervention monitoring. Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit, to efficiently target interventions and suggests evidence is needed to define clinical policy.Trial registrationsThe Finnish Diabetes Prevention study, Helsinki, Finland: ClinicalTrials.gov; NCT00518167 The SLIM diabetes prevention study, Maastricht, The Netherlands: Clinical Trials.gov; NCT00381186 The EDIPS-Newcastle diabetes prevention study, Newcastle upon Tyne, UK: International Standard Randomised Controlled Trial Number; ISRCTN15670600.

Objective: This systematic review aimed to establish a specific evidence-base of diabetes prevention programs for adults at high risk of developing type 2 diabetes (T2D) based on either the Diabetes Prevention Program (DPP) or the Finnish Diabetes Prevention Study (DPS). Methods: The bibliographic databases: Medline, Ovid, Embase, CINAHL, Scopus, Web of Science, Joanna Brigg Institute Library, Cochrane Central Register of Controlled Trials, and grey literature were searched for published articles in the English language from January 1996 to December 2018. This review included only RCTs conducted in community settings focusing on adults at high risk of T2D, utilizing an intervention based on either the DPP or DPS and measuring the incidence of T2D as an outcome. Results: Of 4,964 identified records, eight studies met all inclusion criteria and were suitable for meta-analysis. The meta-analysis revealed positive effects of programs based on either DPP or DPS on prevention T2D in adults at high risk. The pooled incidence rate of T2D in the intervention group was 47% lower than those in the control group (95% CI 9%, 69%). Attending lifestyle change program achieved a pooled mean weight loss of 2.10 kg (95% CI -3.45, -0.74) which was significantly higher than those of the control group. Data in physical activity, dietary and HbA1c were not commonly reported. Although the feasibility of the prevention program was established, this review found a lack of data in enablers and barriers in implementing a diabetes prevention program. Conclusion: The effectiveness of T2D prevention program based on either the DPP or DPS delivered in community settings is evidenced, and the reduction in cumulative incidence of T2D was reported. Nonetheless, further research on enables and barriers associated with increasing physical activity and improving healthy eating is warranted to help sustain the optimal outcomes of the pragmatic diabetes prevention program. Disclosure K.H. Wechkunanukul: None. F. Benton: None. J. McGill: None. S. Ullah: None.

Objective: Ceramides (CER) have been implicated in the pathogenesis of type 2 diabetes (T2D). Here, we assessed baseline plasma CER profiles in relation to incident T2D in the DPP/DPPOS. Methods: Adults at high risk for T2D were randomized in DPP to intensive lifestyle, metformin, or placebo to compare their effects on diabetes incidence, and followed long-term in DPPOS. For this DPP ancillary study, we evaluated 198 randomly selected participants from the DPP placebo group, comprising 100 who had progressed to T2D (P) by DPPOS Year 11 (~15 years after randomization) and 98 non-progressors (NP), frequency matched by sex, age group and race/ethnicity. Plasma levels of 30 CER species, including 10 monohexosylceramides (MHC) and 10 lactosylceramides (LAC), were assayed in DPP baseline specimens using LC-MS/MS. Results: At DPP baseline, mean (&amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; SD) age (51.6 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 8.5 y vs 51.4 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 9.0 y), BMI (34.5 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 7.7 kg/m2 vs. 34.1 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 6. 1 kg/m2), waist circumference, lipids, hsCRP and adiponectin levels were similar, but fasting plasma glucose (FPG) (110 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 8.8 mg/dl vs 104 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 6.3 mg/dl, P&amp;lt;0.0001) and 2-hour plasma glucose (2hPG) (167&amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 15.8 mg/dl vs 160 &amp;lt;u&amp;gt;+&amp;lt;/u&amp;gt; 16.4 mg/dl, P=0.0007) were higher in P vs. NP. Baseline levels of total CER, long-chain CER C20:0 - C26:0 and MHC C22:0 were higher, and LAC C18:0, C20:0 and C26:1 were lower, in P vs. NP, adjusted for age, race, sex, BMI, FPG and 2hPG (P’s = 0.02 to &amp;lt;0.0001). The ratios of CER C26:0/C26:1 (P=0.005) and MHC C24:0/C24:1 (P= 0.008) were higher in P vs. NP. In logistic regression models, baseline plasma ratios of CER C26:0/C26:1 predicted incident T2D: OR 1.26 per 0.1 unit, 95% CI 1.09-1.49, P=0.004, adjusted for baseline age, race, sex, BMI, FPG, and 2hPG Conclusion: Higher baseline plasma levels of long-chain CER and MHC, and lower levels of LAC, were associated with incident T2D during ~15 years of follow-up in the DPP/DPPOS. The saturated-to-unsaturated CER C26:0/C26:1 ratio is a potential biomarker of incident T2D risk among individuals with pre-diabetes. Disclosure P. Asuzu: None. F.B. Stentz: None. J.Y. Wan: None. N. Mandal: None. S. Dagogo-Jack: Consultant; Merck Sharp &amp; Dohme Corp., Medtronic, Bayer Inc. Stock/Shareholder; Aerami.

The purpose of this study was to examine how maintenance session attendance and 6-month weight loss (WL) goal achievement impacted 12-month 5% WL success in older adults participating in a community-based Diabetes Prevention Program (DPP) lifestyle intervention. Data were combined from 2 community trials that delivered the 12-month DPP-based Group Lifestyle Balance (GLB) to overweight/obese adults (mean age = 62 years, 76% women) with prediabetes and/or metabolic syndrome. Included participants (n = 238) attended ≥4 core sessions (months 0-6) and had complete data on maintenance attendance (≥4 of 6 sessions during months 7-12) and 6- and 12-month WL (5% WL goal, yes/no). Multivariate logistic regression was used to estimate the odds of 12-month 5% WL associated with maintenance attendance and 6-month WL. Associations between age (Medicare-eligible ≥65 vs <65 years) and WL and attendance were examined. Both attending ≥4 maintenance sessions and meeting the 6-month 5% WL goal increased the odds of meeting the 12-month 5% WL goal. For those not meeting the 6-month WL goal, maintenance session attendance did not improve odds of 12-month WL success. Medicare-eligible adults ≥65 years were more likely to meet the 12-month WL goal (odds ratio = 3.03, 95% CI, 1.58-5.81) versus <65 years. The results of this study provide important information regarding participant attendance and WL for providers offering DPP-based lifestyle intervention programs across the country who are seeking Medicare reimbursement. Understanding Medicare reimbursement-defined success will allow these providers to focus on and develop strategies to enhance program effectiveness and sustainability.

#1400837: Skewness in Body Fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles

BackgroundType 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost ({mathrm{YLL}}) associated with T2D for Germany in the years 2015 and 2040.MethodsBased on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and {mathrm{YLL}} associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality.ResultsAssuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million {mathrm{YLL}} in the German population aged 40–100 years with prevalent T2D in 2015 and 2040, respectively.ConclusionsGiven expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.