Diabetes Prevention In People Research Articles

Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial

Aims/hypothesisIn sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA.MethodsAdults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat.ResultsIn total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin–placebo) was −0.08 mmol/l (95% CI −0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI −0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was −1.47 kg (95% CI −2.58, −0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs.Conclusions/interpretationBlood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV.Trial registrationThe trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (www.isrctn.com/), registration number: ISCRTN76157257.FundingThis research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.Graphical

Associations of Combined Healthy Lifestyle Factors with Risks of Diabetes, Cardiovascular Disease, Cancer, and Mortality Among Adults with Prediabetes: Four Prospective Cohort Studies in China, the United Kingdom, and the United States

Lifestyle modification is an effective measure for diabetes prevention in people with prediabetes, but its associations with the long-term risks of cardiovascular disease (CVD), cancer, and mortality remain largely uncertain. We aimed to investigate the associations of combined healthy lifestyle factors with these health outcomes among participants with prediabetes. The study included 121 254 people with prediabetes from four prospective cohorts: the Dongfeng-Tongji (DFTJ) cohort and Kailuan study, both from China; the UK Biobank; and the US National Health and Nutrition Examination Survey (NHANES; for mortality analysis only). We documented a total of 18 333 incident diabetes, 10 829 incident CVD, 6926 incident cancer, and 9877 deaths during follow-up. Combined healthy lifestyle scores (scored from 0 to 5) were constructed based on never smoking or quitting smoking for ≥ 10 years, low-to-moderate alcohol drinking, optimal physical activity, healthy diet, and optimal waist circumference. First, Cox proportional-hazards regression models were used to quantify the associations of combined lifestyle score with health outcomes in each cohort; then, multivariable-adjusted hazard ratios (HRs) were pooled via a random-effects model of meta-analysis. Compared with participants with the least healthy lifestyle (a score of 0–1), participants with the healthiest lifestyle (a score of 4–5) had significantly reduced risks of all outcomes. The HRs (95% confidence interval (CI)) were 0.57 (0.48–0.69) for diabetes, 0.67 (0.62–0.73) for CVD, 0.80 (0.73–0.88) for cancer, and 0.54 (0.42–0.70) for mortality. Significant associations were consistently found across subgroups of baseline demographic characteristics and metabolic health status. In conclusion, our pooled analyses of four cohorts from three countries reveal that greater adherence to a healthy lifestyle is associated with considerably lower risks of diabetes and its major complications among adults with prediabetes. These findings provide informative and compelling evidence for establishing clinical guidelines and public health policies.

Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?

ContextOver the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes.Evidence AcquisitionA comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes.Evidence SynthesisLongitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency.ConclusionsResults from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.

839-P: Peripheral and Central Blood Pressure Regulation in Recently Diagnosed Prediabetes

Hypertension is found in up to 90% people with type 2 diabetes. The relationship between blood pressure (BP) (dys)regulation and prediabetes is much less clear. Fifty individuals (mean age [±SD] 42.7±13.1 years, BMI 29.2±7.3 kg/m2) with prediabetes (31 IFG; 19 IGT) and normal BP and 20 age- and BMI-matched healthy persons (40.8±9.6 years, BMI 27.9±6.6 kg/m2) were enrolled into the study. In all participants fasting plasma insulin, adiponectin and interleukin-8 (IL-8) were assessed; and 24-hour ambulatory BP monitoring (ABPM Monitor Schiller BR-102 Plus) and central BP assessment with the applanation tonometry method (SphygmoCor XCEL) were perfomed. ABPM results were similar in both groups: 24-hour systolic, diastolic, mean arterial pressure (MAP) and pulse pressure were 124.1±10.8 and 123.5±7.6; 74.3±7.9 and 74.3±7.0; 89.8±7.2 and 90.4±6.6; 50.5±7.9 i 48.6±5.3 mmHg, respectively (p>0.05). In daytime the respective values were 127.0±11.2 and 126.6±7.4; 75.7±6.5 and 77.2±7.0; 92.4±7.5 and 93.2±6.5; 50.9±8.0 and 48.9±5.5 mmHg, and at nighttime 109.1±21.8 and 109.8±10.5; 61.5±12.7 and 62.7±8.8; 77.1±15.4 and 78.1±9.0; 47.1±11.3 and 46.7±5.4 mmHg (p>0.05). Central systolic, diastolic, end systolic BP, central mean pressure, central pulse height, augmentation index and central stroke volume index were also similar in both groups: 109.3±13.7 and 112.1±14.4, 77.1±9.5 and 80.4±10.7, 99.0±11.7 and 102.1±13.0, 91.3±10.6 and 95.2±11.4, 32.1±9.7 and 31.9±9.4 mmHg, 16.7±13.2 and 15.5±14.3%, 149.5±25.3 and 144.2±29.2 (p>0.05). No significant diffferences in plasma insulin, adiponectin or IL-8 were found between the groups (30.4±25.3 and 26.5±28.8 µIU/ml; 4.86±2.56 and 6.28±3.48 µg/ml; and 25.6±2.58 and 27.9±9.76 pg/ml, respectively, p>0.05). In conclusion, recently diagnosed prediabetes is not associated with any blood pressure abnormalities. Vigorous prevention of diabetes in people with prediabetes should be encouraged as it may lead to maintaining cardiovascular health. Disclosure A. Bogaczewicz-Slowikowska: None. P. Abramczyk: None. K. Cienszkowska: None. E. Janeczko-Sosnowska: None. Z. Gaciong: None. L. Czupryniak: None.

The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized Controlled Trial.

OBJECTIVEThis study tests the effectiveness of expert guidelines for diabetes prevention: lifestyle intervention with addition of metformin, when required, among people with prediabetes.RESEARCH DESIGN AND METHODSThe Diabetes Community Lifestyle Improvement Program (D-CLIP) is a randomized, controlled, translation trial of 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG), or IFG+IGT in Chennai, India. Eligible individuals were identified through community-based recruitment and randomized to standard lifestyle advice (control) or a 6-month, culturally tailored, U.S. Diabetes Prevention Program–based lifestyle curriculum plus stepwise addition of metformin (500 mg, twice daily) for participants at highest risk of conversion to diabetes at ≥4 months of follow-up. The primary outcome, diabetes incidence, was assessed biannually and compared across study arms using an intention-to-treat analysis.RESULTSDuring 3 years of follow-up, 34.9% of control and 25.7% of intervention participants developed diabetes (P = 0.014); the relative risk reduction (RRR) was 32% (95% CI 7–50), and the number needed to treat to prevent one case of diabetes was 9.8. The RRR varied by prediabetes type (IFG+IGT, 36%; iIGT, 31%; iIFG, 12%; P = 0.77) and was stronger in participants 50 years or older, male, or obese. Most participants (72.0%) required metformin in addition to lifestyle, although there was variability by prediabetes type (iIFG, 76.5%; IFG+IGT, 83.0%; iIGT, 51.3%).CONCLUSIONSStepwise diabetes prevention in people with prediabetes can effectively reduce diabetes incidence by a third in community settings; however, people with iIFG may require different interventions.

Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation

Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation

Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation.

BackgroundWe report development of a group-based lifestyle intervention, Let's Prevent, using the UK Medical Research Council (MRC) framework, and delivered by structured education to prevent type 2 diabetes mellitus (T2DM) in people with impaired glucose regulation (IGR) in a UK multi-ethnic population.MethodsDiabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national T2DM programme that meets National Institute for Health and Care Excellence criteria and formed the basis for Let's Prevent. An iterative cycle of initial development, piloting, collecting and collating qualitative and quantitative data, and reflection and modification, was used to inform and refine lifestyle intervention until it was fit for evaluation in a definitive randomized controlled trial (RCT). The programme encouraged IGR self-management using simple, non-technical language and visual aids.ResultsQualitative and quantitative data suggested that intervention resulted in beneficial short-term behaviour change such as healthier eating patterns, improved health beliefs and greater participant motivation and empowerment. We also demonstrated that recruitment strategy and data collection methods were feasible for RCT implementation.ConclusionsLet's Prevent was developed following successful application of MRC framework criteria and the subsequent RCT will determine whether it is feasible, reliable and transferable from research into a real-world NHS primary healthcare setting.Trial RegistrationISRCTN80605705.

Three Patterns of Rising type 2 Diabetes Prevalence in the World: Need to Widen the Concept of Prevention in Individuals into Control in the Community

This paper analyses the patterns of rising type 2 diabetes prevalence in the world with their plausible reasons focusing on control measures. It shows existence of combinations of three patterns of rises, viz. gradual, rapid and accelerated, leading to prevalence of 4-9% now in Europids, 14-20% in migrant or urbanized Asian Indians, Arabs, Chinese, Africans, and Hispanics and above 30-50% in indigenous peoples of Canada, USA, Australia and Pacific regions. It demonstrates that though ageing, sedentary life and obesity of people explain gradual rise in Europids, effects of rapid transition in nutritional status of population and of maternal hyperglycaemia on the risk of offspring developing glucose intolerance further add to rapid and accelerated rises respectively. It recommends that current approach of primary prevention of diabetes in people, particularly with impaired glucose tolerance, advocating modest loss of excess weight and moderate-intensity exercise, be widen into concept of control in community covering rapid and accelerated rises. The control programmes essentially are vigorous educational campaign and planning to improve nutritional status of women of childbearing age in rural and poorer sectors of society and to keep weight of adults within recommended body mass index (BMI) range, like 18.5-22.9 kg/m2 for Asian and other similar populations. The population-based approaches with examples, considering developing countries, are outlined. The paper emphasizes the importance of keeping prepregnancy weight optimum, preferably below the middle of recommended BMI range, to avoid even sub-clinical maternal hyperglycemia, for prevention and control of accelerated rise in any population.

Prevention of Type 2 Diabetes

Changes in the human environment and in human behavior and lifestyle, in conjunction with genetic susceptibility, have resulted in a dramatic increase in the incidence and prevalence of diabetes in the world. The rapid escalation of the number of people with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease demands urgent action on prevention. The Finnish Diabetes Prevention Study and The Diabetes Prevention Program showed that the prevention (or delaying) of T2DM is feasible and effective. Both of these trials led to a reduction of 58% in the conversion to diabetes in subjects with impaired glucose tolerance. Compared to lifestyle changes, drug treatment in the prevention of diabetes in people at high risk for T2DM has been less beneficial. Metformin (31%) or acarbose (25%) treatment obtained only about a half of the reduction in the conversion to diabetes compared to lifestyle changes. These drugs require monitoring, and have significant side-effects. Also the effect of orlistat (37%) did not reach the effect of lifestyle modification. Results of the Troglitazone in Prevention of Diabetes study are suggestive for the prevention, but the trial was too small, and included only one ethnic group (Hispanic) and one gender (women). On the basis of the evidence available, we do not have a definite proof that T2DM is prevented in any of these trials. However, we can safely conclude that the current evidence strongly favors the notion that lifestyle changes are the primary means to tackle the epidemic of T2DM.