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      Novel subgroups of type 2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis: the INSPIRED study

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          Abstract

          Introduction

          Type 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering.

          Research design and methods

          From a network of 50 diabetes centers across nine states of India, we selected 19 084 individuals with type 2 diabetes (aged 10–97 years) with diabetes duration of less than 5 years at the time of first clinic visit and performed k-means clustering using the following variables: age at diagnosis, body mass index, waist circumference, glycated hemoglobin, serum triglycerides, serum high-density lipoprotein cholesterol and C peptide (fasting and stimulated). This was then validated in a national epidemiological data set of representative individuals from 15 states across India.

          Results

          We identified four clusters of patients, differing in phenotypic characteristics as well as disease outcomes: cluster 1 (Severe Insulin Deficient Diabetes, SIDD), cluster 2 (Insulin Resistant Obese Diabetes, IROD), cluster 3 (Combined Insulin Resistant and Deficient Diabetes, CIRDD) and cluster 4 (Mild Age-Related Diabetes, MARD). While SIDD and MARD are similar to clusters reported in other populations, IROD and CIRDD are novel clusters. Cox proportional hazards showed that SIDD had the highest hazards for developing retinopathy, followed by CIRDD, while CIRDD had the highest hazards for kidney disease.

          Conclusions

          Compared with previously reported clustering, we show two novel subgroups of type 2 diabetes in the Asian Indian population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.

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          Most cited references13

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          Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR–INDIAB population-based cross-sectional study

          Previous studies have not adequately captured the heterogeneous nature of the diabetes epidemic in India. The aim of the ongoing national Indian Council of Medical Research-INdia DIABetes study is to estimate the national prevalence of diabetes and prediabetes in India by estimating the prevalence by state.
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            Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) eye study, I.

            To assess the prevalence of diabetic retinopathy (DR) in type 2 diabetic subjects in urban India using four-field stereo color photography. The Chennai Urban Rural Epidemiology Study (CURES) is a population-based study conducted on a representative population of Chennai (formerly Madras) city in South India. Individuals > or =20 years in age (n = 26,001) were screened for diabetes. Of the 1529 known diabetic subjects, 1382 (90.4%) participated in the study. Subjects with newly detected diabetes (n = 354) by the oral glucose tolerance test (OGTT) also consented to participate in the study. All the subjects underwent four-field stereo color photography, and retinopathy was graded in the color fundus photographs according to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. The overall prevalence of DR in the population was 17.6% (95% confidence interval [CI]: 15.8-19.5), which included 20.8% (95% CI: 18.7-23.1) in known diabetic subjects and 5.1% (95% CI: 3.1-8.0) in subjects with newly detected diabetes. The prevalence of DR was significantly higher in men than in women (21.3% vs. 14.6%; P < 0.0001) and among subjects with proteinuria (P = 0.002). Logistic regression analysis showed that for every 5-year increase in the duration of diabetes, the risk for DR increased 1.89-fold (95% CI: 1.679-2.135; P < 0.0001). For every 2% elevation of glycated hemoglobin (HbA1c), the risk for DR increased by a factor of 1.7 (95% CI: 1.545-1.980; P < 0.0001). This study shows that the prevalence of diabetic retinopathy is lower in urban South Indians than in other ethnic groups. However, due to the large number of diabetic subjects, DR is likely to pose a public health burden in India; hence, routine retinal examination is mandatory to detect DR in the early stages.
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              Insulin resistance in chronic kidney disease: a systematic review.

              Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.
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                Author and article information

                Journal
                BMJ Open Diabetes Res Care
                BMJ Open Diabetes Res Care
                bmjdrc
                bmjdrc
                BMJ Open Diabetes Research & Care
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2052-4897
                2020
                17 August 2020
                : 8
                : 1
                : e001506
                Affiliations
                [1 ]departmentDiabetology , Madras Diabetes Research Foundation , Chennai, Tamil Nadu, India
                [2 ]departmentDiabetology , Dr Mohan’s Diabetes Specialities Centre Gopalapuram , Chennai, Tamil Nadu, India
                [3 ]departmentData Management , Madras Diabetes Research Foundation , Chennai, Tamil Nadu, India
                [4 ]departmentDivision of Population Health and Genomics , University of Dundee School of Medicine , Dundee, Dundee, UK
                [5 ]departmentEpidemiology , Madras Diabetes Research Foundation , Chennai, Tamil Nadu, India
                [6 ]departmentDivision of Cardiovascular and Diabetes Medicine , University of Dundee , Dundee, Dundee, UK
                Author notes
                [Correspondence to ] Dr Viswanathan Mohan; drmohans@ 123456diabetes.ind.in
                Author information
                http://orcid.org/0000-0002-4843-1374
                http://orcid.org/0000-0001-5038-6210
                Article
                bmjdrc-2020-001506
                10.1136/bmjdrc-2020-001506
                7437708
                32816869
                d77cbc2a-6594-42ea-8d32-fbc18077c7f2
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 25 April 2020
                : 04 June 2020
                : 02 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Award ID: 16/136/102
                Categories
                Epidemiology/Health services research
                1506
                1867
                Custom metadata
                unlocked

                diabetes mellitus, type 2,india,diabetes complications

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