A Consensus of Key Opinion Leaders on the Management of Pre-diabetes in the Asia-Pacific Region.

The Asia-Pacific region carries a high disease burden, with over half of the global diabetic population residing in this region. Increasing evidence shows that without targeted intervention, the progression from impaired glucose tolerance (IGT) to type 2 diabetes occurs more frequently in Asians compared with Caucasians. Furthermore, IGT is independently associated with an increased risk of cardiovascular disease, and should be managed as early as possible. Because diabetes is now a major public health issue, strategies aimed at prevention and treatment are urgently required. Lifestyle modification, including weight loss, dietary changes and increased physical activity, play a major role in controlling the disease. Significant evidence also supports the effectiveness of a combination of lifestyle modification and pharmacologic therapy, such as metformin, in delaying the onset of diabetes. Although the importance of lifestyle interventions is well recognized throughout Asia, many countries do not have formal recommendations to guide the diagnosis and management of individuals at risk of progression to diabetes. At a recent regional meeting, experts from the Asian region convened to develop consensus recommendations to guide clinicians in the management of Asian patients with pre-diabetes. These consensus recommendations provide a clear and concise approach to the management of individuals with IGT based on the available evidence and current best clinical practice.

Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c and retinopathy in a multiethnic Asian population.

CONTEXT: Hemoglobin A1c (HbA1c) ≥ 6.5% (47.5 mmol/mol) has recently been included as a criterion for the diagnosis of diabetes mellitus. It is unclear whether this criterion is appropriate in Asians. OBJECTIVE: To examine the relationship between HbA1c and diabetes-specific moderate retinopathy in Asian ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: Four independent population-based cross-sectional studies (2004-2011) in Singapore representing the three major Asian ethnic groups (n = 13 170 adults aged ≥ 25 y: Chinese, 5834; Malays, 3596; and Indians, 3740). MAIN OUTCOME: Moderate retinopathy was assessed from digital retinal photographs and defined as a level >43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve for detecting moderate retinopathy were compared across ethnic groups at different HbA1c cut-points. RESULTS: HbA1c levels were higher in Indians and Malays compared to Chinese (P < .001). The prevalence of moderate retinopathy below HbA1c <6.5% was <1% in all ethnic groups. At HbA1c ≥ 6.5%, the sensitivity for detecting moderate retinopathy was lower in Chinese subjects compared to Indians and Malays (75.8 vs 86.0 and 85.3%), but specificity (89.7 vs 71.9 and 76.3%) was higher; however, positive predictive value and negative predictive value were similar among Chinese, Indians, and Malays (10.5, 12.3, 12.4%; and 99.6, 99.1, 99.2%, respectively). The AUCs were similar across all three ethnic groups (0.861, 0.851, and 0.853). CONCLUSIONS: Our study supports the use of HbA1c for diagnosing diabetes in Asians. Despite some interethnic variation in the relationship of HbA1c and retinopathy, a cut-point of 6.5% performs reasonably well in the three major Asian ethnic groups.

The Prevalence of Gestational Diabetes Mellitus Among Asian Females is Lower Using the New 2013 World Health Organization Diagnostic Criteria.

OBJECTIVE: To determine the impact of the new 2013 World Health Organization (WHO) criteria for gestational diabetes mellitus (GDM) diagnosis on GDM prevalence and pregnancy outcomes in Asian ethnic groups compared to the 1999 WHO criteria. METHODS: A retrospective cohort study included 855 pregnant females of Chinese, Malay, and Asian Indian ethnicity at high risk of GDM who underwent 75-g oral glucose tolerance tests (OGTTs) between July 2008 and June 2010 in a tertiary center in Singapore. GDM prevalence, reclassification, and pregnancy outcomes were determined using the 2013 and 1999 diagnostic cutoffs for fasting and 2-hour postglucose (PG) values. RESULTS: The prevalence of GDM was reduced from 28.8% to 21.1% when the 2013 criteria were used. Overall, 10.2% subjects were reclassified from GDM to normal using the 2013 criteria, and 2.6% were reclassified from normal to GDM, giving a net reclassification rate of 12.8%. Reclassification from GDM to normal was greatest among Chinese, followed by Asian Indians, but the prevalence rate was unchanged among Malays. Babies of mothers who were reclassified from normal to GDM were more likely to have birth weight >95th centile and shoulder dystocia. CONCLUSION: The prevalence of GDM was reduced when the 2013 criteria were used, with the greatest reduction seen among Chinese, followed by Asian Indians. Lowering the fasting cutoff as per the new criteria identified a select group of patients who might benefit from GDM treatment. However, raising the 2-hour PG cutoff would miss a significant number of patients who might potentially benefit from GDM treatment.

Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 × 10(-23)], HBS1L/MYB [8.5 × 10(-15)], MYO9B [9.0 × 10(-12)], and CYBA [1.1 × 10(-8)] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA1c (≥6.5%), 36.1% had HbA1c <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA1c as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA1c for diagnosing diabetes in these populations.

Unusual presentation of pheochromocytoma with ischemic sigmoid colitis and stenosis.

A 45-year-old woman with poorly controlled hypertension and diabetes mellitus presented with left iliac fossa pain, constipation alternating with diarrhea, and weight loss. She had been diagnosed with idiopathic cardiomyopathy five years previously. Echocardiogram had shown a left ventricular ejection fraction (LVEF) of 35%; coronary angiogram was normal. Colonoscopy revealed sigmoid colitis with stenosis. Abdominal computed tomography revealed a 5 cm right adrenal tumor. Twenty-four hour urinary free catecholamines and fractionated metanephrine excretion values were elevated, confirming pheochromocytoma. Her colitis resolved after one month of adrenergic blockade. Repeat echocardiogram showed improvement of LVEF to 65%. After laparoscopic right adrenalectomy, the patient's hypertension resolved, and diabetic control improved. Timely management avoided further morbidity and potential mortality in our patient.

Evidence of autoantibodies to glutamic acid decarboxylase in oral fluid of type 1 diabetic patients.

Circulating antibodies to glutamic acid decarboxylase (GADab) are a major indicator for autoimmune destruction of pancreatic islet cells (type 1 diabetes). Previously reported detection of GADab in oral fluid, however, was assayed by enzyme-linked immunosorbent assay (ELISA) with low diagnostic sensitivity and high non-specific binding. We re-assessed oral fluid GADab detection using a different sampling technique and a more robust assay. Type 1 diabetic subjects (n = 32; mean age +/- SD: 13.9 +/- 3.7 years) provided Orasure oral fluid and venous blood samples. Orasure collections were assayed for total immunoglobulin G (IgG), then concentrated to 1/10 of their volume using mini-centrifugal protein concentrators. All samples were assayed by a GAD65 antibody radio-immunoprecipitation method. Oral fluid antibodies were detected ( > 99th percentile of radio-binding (%counts per min (%cpm)) for seronegatives) in 10/16 seropositive subjects, with %cpm (median: 6.4%; range: 4.6-25.8) significantly greater (P < 0.001) than for seronegatives (median: 4.7%; range: 3.4-5.7). A highly significant correlation (Spearman's rho: 0.85; P<0.001) was demonstrated between %cpm of concentrates and respective serum titres for seropositive diabetics. Median IgG concentration of Orasure collections was 22.8 mg/l (range: 9.4-168.0). GADab recovery from Orasure collectors was estimated at 90%. This is the first confirmatory detection of diabetes-specific autoimmune markers in oral fluid. Acceptable correlation between concentrated oral fluid radio-binding and serum titre was achieved. Improved antibody recovery and assay re-optimisation could provide a basis for more extensive studies that may lead to an alternative non-invasive screening method for pre-clinical autoimmune diabetes.