Black African men with early type 2 diabetes have similar muscle, liver and adipose tissue insulin sensitivity to white European men despite lower visceral fat.

AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in black African than white European populations although, paradoxically, black African individuals present with lower levels of visceral fat, which has a known association with insulin resistance. Insulin resistance occurs at a tissue-specific level; however, no study has simultaneously compared whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men. We hypothesised that, in those with early type 2 diabetes, black (West) African men (BAM) have greater hepatic and adipose tissue insulin sensitivity, compared with white European men (WEM), because of their reduced visceral fat. METHODS: Eighteen BAM and 15 WEM with type 2 diabetes underwent a two-stage hyperinsulinaemic-euglycaemic clamp with stable glucose and glycerol isotope tracers to assess tissue-specific insulin sensitivity and a magnetic resonance imaging scan to assess body composition. RESULTS: We found no ethnic differences in whole body, skeletal muscle, hepatic or adipose tissue insulin sensitivity between BAM and WEM. This finding occurred in the presence of lower visceral fat in BAM (3.72 vs 5.68 kg [mean difference -1.96, 95% CI -3.30, 0.62]; p = 0.01). There was an association between skeletal muscle and adipose tissue insulin sensitivity in WEM that was not present in BAM (r = 0.78, p < 0.01 vs r = 0.25 p = 0.37). CONCLUSIONS/INTERPRETATION: Our data suggest that in type 2 diabetes there are no ethnic differences in whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men, despite differences in visceral adipose tissue, and that impaired lipolysis may not be contributing to skeletal muscle insulin resistance in men of black African ethnicity.

Ethnic differences in intrahepatic lipid and its association with hepatic insulin sensitivity and insulin clearance between men of black and white ethnicity with early type 2 diabetes.

Intrahepatic lipid (IHL) is linked with reduced hepatic insulin sensitivity and insulin clearance. Despite their high risk for type 2 diabetes (T2D), there have been limited investigations of these relationships in black populations. We investigated these relationships in 18 white European (WE) and 18 black West African (BWA) men with T2D <5 years. They underwent magnetic resonance imaging to quantify IHL, a hyperinsulinemic euglycaemic clamp with [6,6 2 H2 ] glucose infusion to assess hepatic insulin sensitivity and a hyperglycaemic clamp to assess insulin clearance. BWA men had lower IHL than WE men (3.7 [5.3] vs 6.6 [10.6]%, P = 0.03). IHL was inversely associated with basal hepatic insulin sensitivity in WE but not BWA men (BWA: r = -0.01, P = 0.96; WE: r = -0.72, P = 0.006) with a significant interaction by ethnicity (Pinteraction = 0.05); however, IHL was not associated with % suppression of endogenous glucose production by insulin in either ethnicity. IHL showed a trend to an association with insulin clearance in BWA only (BWA: r = -0.42, P = 0.09; WE: r = -0.14, P = 0.58). The lack of association between IHL and hepatic insulin sensitivity in BWA men indicates IHL may play a lesser detrimental role in T2D in BWA men.

Ethnic differences in insulin secretory function between black African and white European men with early type 2 diabetes.

AIM: To test the hypothesis that men of black (West) African ethnicity (black African men [BAM]) with early type 2 diabetes (T2D) would have greater insulin secretory deficits compared with white European men (WEM), following prediabetic hypersecretion. METHODS: In 19 BAM and 15 WEM, matched for age, body mass index and duration of diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test). RESULTS: With similar post-challenge glucose responses, BAM had lower second-phase C-peptide responses to intravenous glucose (BAM 70.6 vs WEM 115.1 nmol/L/min [ratio of geometric mean 0.55, 95% confidence interval {CI} 0.37, 0.83]; P = .006) and to oral glucose (BAM 65.4 vs WEM 88.5 nmol/L/min [mean difference -23.2, 95% CI -40.0, -6.3]; P = .009). Peripheral insulin response in BAM to oral glucose was preserved (BAM 47.4 vs WEM 59.4 nmol/L/min [ratio of geometric mean 0.89, 95% CI 0.59, 1.35]; P = .566), with relative reductions in insulin clearance (BAM 506.2 vs WEM 630.1 mL/m2 BSA/min [mean difference -123.9, 95% CI -270.5, 22.6]; P = .095), associated with enhanced incretin responses (gastric inhibitory polypeptide incremental area under the curve: BAM 46.8 vs WEM 33.9 µg/L/min [mean difference 12.9, 95% CI 2.1, 23.7]; P = .021). CONCLUSIONS: In early T2D, BAM had significantly lower insulin secretory responses to intravenous and oral stimulation than WEM. Lower insulin clearance, potentially driven by increased incretin responses, may act to preserve peripheral insulin concentrations. Tailoring early management strategies to reflect distinct ethnic-specific pathophysiology may improve outcomes in this high-risk population.

All-cause cancer mortality over 15 years in multi-ethnic Mauritius: the impact of diabetes and intermediate forms of glucose tolerance.

There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic cohort from the developing nation of Mauritius. Population-based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h-PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98-2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

Diagnosing type 2 diabetes using Hemoglobin A1c: a systematic review and meta-analysis of the diagnostic cutpoint based on microvascular complications.

AIMS: Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes. METHODS: Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of < 6.0% (< 42 mmol/mol), 6.0-6.4% (42-47 mmol/mol) and ≥ 6.5% (≥ 48 mmol/mol). Random-effects meta-analyses were conducted for retinopathy, nephropathy and neuropathy prevalence stratified by HbA1c categories. Random-effects multivariable meta-regression was conducted to identify predictors of retinopathy prevalence and sources of between-study heterogeneity. RESULTS: Pooled mean prevalence was: 4.0%(95% CI: 3.2-5.0%) for retinopathy, 10.5% (95% CI: 4.0-19.5%) for nephropathy, 2.5% (95% CI: 1.1-4.3%) for neuropathy. Mean prevalence when stratified for HbA1c < 6.0%, 6.0-6.4% and ≥ 6.5% was: retinopathy: 3.4% (95% CI: 1.8-5.4%), 2.3% (95% CI: 1.6-3.2%) and 7.8%(95% CI: 5.7-10.3%); nephropathy: 7.1% (95% CI: 1.7-15.9%), 9.6% (95% CI: 0.8-26.4%) and 17.1% (95% CI: 1.0-46.9%); neuropathy: 2.1% (95% CI: 0.0-6.8%), 3.4% (95% CI: 0.0-11.6%) and 2.8% (95% CI: 0.0-12.8%). Multivariable meta-regression showed HbA1c ≥ 6.5% (OR: 4.05; 95% CI: 1.92-8.57%), age > 55 (OR: 3.23; 95% CI 1.81-5.77), and African-American race (OR: 10.73; 95% CI: 4.34-26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran's Q-statistic p < 0.0001). CONCLUSIONS: The prevalence of nephropathy and moderate retinopathy was increased in subjects with HbA1c values ≥ 6.5% confirming the high specificity of this value for diagnosing T2DM; however, at HbA1c < 6.5% retinopathy increased at age > 55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold.

COVID-19 and metabolic disease: mechanisms and clinical management.

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

Early emergence of ethnic differences in type 2 diabetes precursors in the UK: the Child Heart and Health Study in England (CHASE Study).

BACKGROUND: Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood. METHODS AND FINDINGS: We performed a cross-sectional survey of 4,796 children aged 9-10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference -2.9, 95% CI -4.5 to -1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased. CONCLUSIONS: Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention.

Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK.

BACKGROUND: Diabetes prevalence is increasing. The Finnish Diabetes Prevention Study (DPS) showed a 58% reduction in Type 2 Diabetes (T2D) incidence in adults with impaired glucose tolerance (IGT). The European Diabetes Prevention Study (EDIPS) extends the DPS to different European populations, using the same study design. In the Newcastle arm of this study (EDIPS-Newcastle), we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence. METHODS: We recruited 102 participants (42 men and 60 women, mean age 57 years, mean BMI 34 kgm-2) with IGT to EDIPS-Newcastle and randomised to Intervention and usual care Control groups. The intervention included individual motivational interviewing aimed at: weight reduction, increase in physical activity, fibre and carbohydrate intake and reduction of fat intake (secondary outcomes). The primary outcome was diagnosis of T2D. RESULTS: Mean duration of follow-up was 3.1 years. T2D was diagnosed in 16 participants (I = 5, C = 11). Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group. The overall incidence of diabetes was reduced by 55% in the Intervention-group, compared with the Control-group: RR 0.45 (95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D. CONCLUSION: Our results are consistent with other diabetes prevention trials. This study was designed as part of a larger study and although the sample size limits statistical significance, the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT. In explanatory analysis small sustained beneficial changes in weight, physical activity or dietary factors were associated with reduction in T2D incidence. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry (ISRCTN) Registry number: ISRCTN15670600. (http://www.controlled-trials.com/isrctn/search.html?srch=15670600&sort=3&dir=desc&max=10).

Associations Between Pancreatic Lipids and ß-Cell Function in Black African and White European Men With Type 2 Diabetes.

CONTEXT: Intrapancreatic lipid (IPL) has been linked to ß-cell dysfunction. Black populations disproportionately develop type 2 diabetes (T2D) and show distinctions in ß-cell function compared with white populations. OBJECTIVE: We quantified IPL in white European (WE) and black West African (BWA) men with early T2D and investigated the relationships between IPL and ß-cell insulin secretory function (ISF). DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional assessment of 18 WE and 19 BWA middle-age men with early T2D as part of the South London Diabetes and Ethnicity Phenotyping study. MAIN OUTCOME MEASURES: The participants underwent Dixon MRI to determine IPL in the pancreatic head, body, and tail and subcutaneous and visceral adipose tissue volumes. Modeled first- and second-phase ISFs were comprehensively determined using C-peptide measurements during a 3-hour meal tolerance test and a 2-hour hyperglycemic clamp test. RESULTS: The WE men had greater mean IPL levels compared with BWA men (P = 0.029), mainly owing to greater IPL levels in the pancreatic head (P = 0.009). The mean IPL level was inversely associated with orally stimulated first-phase ISF in WE but not BWA men (WE, r = -0.554, P = 0.026; BWA, r = -0.183, P = 0.468). No association was found with orally stimulated second-phase ISF in either WE or BWA men. No associations were found between the mean IPL level and intravenously stimulated ISF. CONCLUSIONS: The IPL levels were lower in BWA than WE men with early T2D, and the lack of inverse association with first-phase ISF in BWA men indicates that IPL might be a less important determinant of the development of T2D in BWA than in WE men.

A prospective study of glycemia, body size, insulin resistance and the risk of hypertension in Mauritius.

OBJECTIVE: To estimate the associations between new-onset hypertension and glycemia, insulin resistance, and overall and regional adiposity in a prospective study conducted in Mauritius. RESEARCH DESIGN AND METHODS: Three thousand five hundred and eighty-one adults without hypertension, pregnancy, or known diabetes at baseline (1987) were followed for incident hypertension in 1992 and 1998, (systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg or antihypertensive medication treatment). Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load, fasting insulin, BMI, waist circumference, smoking, alcohol use, exercise, and demographic information. Insulin sensitivity was estimated by the computerized homeostasis model assessment (HOMA2) program. RESULTS: In multivariable logistic models that included age, gender, ethnicity, alcohol use, exercise, education, systolic blood pressure, diastolic blood pressure, homeostasis model assessment, fasting plasma glucose, 2-h plasma glucose, BMI, and waist circumference, the independent predictors of incident hypertension by time of follow-up were (odds ratio for a 1 SD increase; 95% confidence interval): 1992 - age (1.73; 1.47-2.03), Creole ethnicity (1.42; 1.04-1.94), 2-h plasma glucose (1.26; 1.04-1.51); 1998 - age (1.60; 1.40-1.83) and BMI (1.33; 1.05-1.69). Also, systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points. CONCLUSION: Risk factor patterns depended on duration of follow-up. Over 5 years, hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment, while over 11 years, incident hypertension was related to BMI but not waist circumference, 2-h plasma glucose, or homeostasis model assessment. These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference, fasting plasma glucose, or insulin resistance in the development of hypertension in Mauritius.

Association between type 2 diabetes mellitus and disability: What is the contribution of diabetes risk factors and diabetes complications?

BACKGROUND: The aim of this study was to evaluate the association between type 2 diabetes and disability in Mauritius and to assess the extent to which the effect of diabetes is explained by diabetes risk factors and concomitant complications. METHODS: Data from a national survey in the multiethnic nation of Mauritius, which comprises South Asians and African Creoles, were analyzed. Disability was measured using the Katz activities of daily living questionnaire in participants aged >50 years. RESULTS: Among 3692 participants, 487 (13.2%) had some level of disability. Diabetes was associated with significantly higher risk of disability (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.34-2.08). After adjusting for demographic, behavioral, and metabolic factors, as well as comorbidities, disability was significantly associated with diabetes among African Creoles (OR 2.03; 95% CI 1.16-3.56), but not South Asians (OR 1.27; 95% CI 0.98-1.66). Obesity explained much of the association between diabetes and disability (excess percentage of risk: 26.3% in South Asians and 12.1% in African Creoles). Obesity, history of cardiovascular disease (CVD), asthma-like symptoms, and depression together explained 46.5% and 29.0% of the excess risk in South Asians and African Creoles, respectively. CONCLUSIONS: Diabetes is associated with a 67% increased risk of disability. Diabetes risk factors and comorbidities explain more of the association between diabetes and disability among South Asians than Africans. Obesity and history of CVD explained the largest percentage of the relationship between diabetes and disability, indicating that weight and CVD management may be helpful in controlling disability related to diabetes.

Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).

BACKGROUND: Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. METHODS: Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) FINDINGS: The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001). INTERPRETATION: GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.

Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: A cross-sectional multiethnic study.

AIMS: Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. METHODS: We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0-6.4% (42-47 mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70) and other/mixed (n=103) groups were distinguished and measurements included fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). RESULTS: Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10-3.42), p 0.03) and only LDL-c with IFG (FPG 5.6 to <7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant independent associations with cardiometabolic risk factors when categories of impaired fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. CONCLUSION: In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: a Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m2) and in those with class II obesity (BMI 35.0-39.9 kg/m2) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m2 for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Epidemiology of Diabetes-Status of a Pandemic and Issues Around Metabolic Surgery.

The number of people with diabetes worldwide has more than doubled during the past 20 years. One of the most worrying features of this rapid increase is the emergence of type 2 diabetes in children, adolescents, and young adults. Although the role of traditional risk factors for type 2 diabetes, such as genetic, lifestyle, and behavioral risk factors, has been given attention, recent research has focused on identifying the contributions of epigenetic mechanisms and the effect of the intrauterine environment. Epidemiological data predict an inexorable and unsustainable increase in global health expenditure attributable to diabetes, so disease prevention should be given high priority. An integrated approach is needed to prevent type 2 diabetes and must recognize its heterogeneity. Future research needs to be directed at improved understanding of the potential role of determinants, such as the maternal environment and other early life factors, as well as changing trends in global demography, to help shape disease prevention programs. Equally important is a better understanding of the role of metabolic surgery in helping to address the management both of persons with type 2 diabetes and of those persons in the community who are at higher risk for type 2 diabetes, particularly in emerging nations where the diabetes epidemic is in full flight.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Glucose-independent ethnic differences in HbA1c in people without known diabetes.

OBJECTIVE: To determine whether glucose-independent differences in HbA1c exist between people of African, South Asian, and Chinese ethnicities. RESEARCH DESIGN AND METHODS: Data from 6,701 people aged 19-78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA1c, plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history. RESULTS: Mean HbA1c, after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA1c, was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P < 0.001), Chinese (5.7%, P < 0.001), or Africans from the main island of Mauritius (5.7%, P < 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8-10.0); HbA1c 17.3% (15.3-19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups. CONCLUSIONS: People of African ethnicity from Rodrigues have higher HbA1c than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.