Mala Dharmalingam

Effectiveness of a Multicomponent Quality Improvement Strategy to Improve Achievement of Diabetes Care Goals: A Randomized, Controlled Trial

BACKGROUND Achievement of diabetes care goals is suboptimal globally. Diabetes-focused quality improvement (QI) is effective but remains untested in South Asia. OBJECTIVE To compare the effect of a multicomponent QI strategy versus usual care on cardiometabolic profiles in patients with poorly controlled diabetes. DESIGN Parallel, open-label, pragmatic randomized, controlled trial. (ClinicalTrials.gov: NCT01212328). SETTING Diabetes clinics in India and Pakistan. PATIENTS 1146 patients (575 in the intervention group and 571 in the usual care group) with type 2 diabetes and poor cardiometabolic profiles (glycated hemoglobin [HbA1c] level ≥8% plus systolic blood pressure [BP] ≥140 mm Hg and/or low-density lipoprotein cholesterol [LDLc] level ≥130 mg/dL). INTERVENTION Multicomponent QI strategy comprising nonphysician care coordinators and decision-support electronic health records. MEASUREMENTS Proportions achieving HbA1c level less than 7% plus BP less than 130/80 mm Hg and/or LDLc level less than 100 mg/dL (primary outcome); mean risk factor reductions, health-related quality of life (HRQL), and treatment satisfaction (secondary outcomes). RESULTS Baseline characteristics were similar between groups. Median diabetes duration was 7.0 years; 6.8% and 39.4% of participants had preexisting cardiovascular and microvascular disease, respectively; mean HbA1c level was 9.9%; mean BP was 143.3/81.7 mm Hg; and mean LDLc level was 122.4 mg/dL. Over a median of 28 months, a greater percentage of intervention participants achieved the primary outcome (18.2% vs. 8.1%; relative risk, 2.24 [95% CI, 1.71 to 2.92]). Compared with usual care, intervention participants achieved larger reductions in HbA1c level (-0.50% [CI, -0.69% to -0.32%]), systolic BP (-4.04 mm Hg [CI, -5.85 to -2.22 mm Hg]), diastolic BP (-2.03 mm Hg [CI, -3.00 to -1.05 mm Hg]), and LDLc level (-7.86 mg/dL [CI, -10.90 to -4.81 mg/dL]) and reported higher HRQL and treatment satisfaction. LIMITATION Findings were confined to urban specialist diabetes clinics. CONCLUSION Multicomponent QI improves achievement of diabetes care goals, even in resource-challenged clinics. PRIMARY FUNDING SOURCE National Heart, Lung, and Blood Institute and UnitedHealth Group.

Oxidative Stress in Obesity and Metabolic Syndrome in Asian Indians

Oxidative Stress in Obesity and Metabolic Syndrome in Asian Indians Oxidative stress is associated with the individual components of metabolic syndrome and has been implicated in the development of complications of these metabolic disorders. In this study oxidative stress levels have been compared in obese Indians (a high-risk population for diabetes and cardiovascular disorders) with and without metabolic syndrome. 30 adult normotensive, normoglycemic obese subjects and 35 adults with metabolic syndrome of either sex with BMI >23 kg/m2 were compared with 30 adult, healthy volunteers with BMI <23 kg/m2. Anthropometric parameters, blood pressure, biochemical parameters, hydroperoxides levels and total antioxidant capacity were estimated. The obese groups with and without metabolic syndrome had significantly increased anthropometric parameters like waist circumference and index of central obesity and aqueous phase hydroperoxides when compared with normal controls. The metabolic syndrome group also had significantly increased blood sugar levels, lipid profile and hydroperoxide levels when compared to obese or control groups. There was no alteration in the total antioxidant capacity in any of the groups. The Triglyceride/HDL-Cholesterol ratio (>3), a surrogate marker of insulin resistance, indicates insulin resistance in the metabolic syndrome group. The anthropometric profile, insulin resistance and oxidative stress seen in obesity are further elaborated in metabolic syndrome. Thus, the early identification of high-risk individuals based on anthropometric parameters, lipid profile, insulin resistance and indices of oxidative stress may help to prevent the development of complications of metabolic syndrome. Oksidativni Stres u Gojaznosti i Metaboličkom Sindromu Kod Indijaca Oksidativni stres dovodi se u vezu sa pojedinačnim komponentama metaboličkog sindroma i povezan je sa razvojem komplikacija u metaboličkim poremećajima. U ovoj studiji upoređeni su nivoi oksidativnog stresa kod gojaznih Indijaca (populaciji sa visokim rizikom za razvoj dijabetesa i kardiovaskularnih poremećaja) sa i bez metaboličkog sindroma. Trideset odraslih normotenzivnih, normoglikemičnih gojaznih ispitanika i 35 odraslih osoba sa metaboličkim sindromom oba pola sa ITM >23 kg/m2 poređeno je sa 30 odraslih zdravih dobrovoljaca sa ITM <23 kg/m2. Ispitivani su antropometrijski parametri, krvni pritisak, biohemijski parametri, nivoi hidroperoksida i ukupni antioksidantni kapacitet. U gojaznim grupama sa i bez metaboličkog sindroma antropometrijski parametri kao što su obim struka i indeks centralne gojaznosti i aqueous phase hidroperoksidi bili su značajno povišeni u poređenju sa kontrolnim subjektima. Grupa sa metaboličkim sindromom takođe je imala značajno povišene nivoe šećera u krvi, lipidni profil i nivoe hidroperoksida u poređenju sa gojaznom ili kontrolnom grupom. Ni u jednoj grupi nije bilo promena u ukupnom antioksidantnom kapacitetu. Odnos trigliceridi/HDL holesterol (>3), kao surogat marker insulinske rezistencije, ukazuje na rezistenciju na insulin u grupi sa metaboličkim sindromom. Antropometrijski profil, insulinska rezistencija i oksidativni stres prisutni u gojaznosti dalje se razvijaju u metaboličkom sindromu. Otud rana identifikacija osoba sa visokim rizikom na osnovu antropometrijskih parametara, lipidnog profila, insulinske rezistencije i indeksa oksidativnog stresa može doprineti sprečavanju razvoja komplikacija metaboličkog sindroma.

Improving diabetes care: Multi-component cardiovascular disease risk reduction strategies for people with diabetes in South Asia—The CARRS Multi-center Translation Trial

AIMS Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in people with diabetes in South Asia. The CARRS Translation Trial tests the effectiveness, cost-effectiveness, and sustainability of a clinic-based multi-component CVD risk reduction intervention among people with diabetes in India and Pakistan. METHODS We randomly assigned 1146 adults with diabetes recruited from 10 urban clinic sites, to receive usual care by physicians or to receive an integrated multi-component CVD risk reduction intervention. The intervention involves electronic health record management, decision-support prompts to the healthcare team, and the support of a care coordinator to actively facilitate patient and provider adherence to evidence-based guidelines. The primary outcome is a composite of multiple CVD risk factor control (blood glucose and either blood pressure or cholesterol, or all three). Other outcomes include control of the individual CVD risk factors, process and patient-centered measures, cost-effectiveness, and acceptability/feasibility. CONCLUSION The CARRS Translation Trial tests a low-cost diabetes care delivery model in urban South Asia to achieve comprehensive cardio-metabolic disease case-management of high-risk patients (clinicaltrials.gov number: NCT01212328).

Results from a dietary survey in an Indian T2DM population: a STARCH study

Objective To assess the dietary total and complex carbohydrate (CHO) contents in type-2 diabetes mellitus (T2DM) participants in India. Setting We enrolled 796 participants in this cross-sectional, single-visit, multicentre, two-arm, single-country survey. Participants were enrolled from 10 specialty endocrinology/dialectology centres from five regions of India. Participants A total of 796 participants (Asian) were enrolled in this study (385, T2DM and 409, non-T2DM). Key inclusion criteria—male or female ≥18 years, diagnosed with T2DM ≥12 months (T2DM), and not on any diet plan (non-T2DM). Study outcome Primary outcome was to find out the percentage of total energy intake as simple and complex CHO from total CHO. Secondary outcomes were to find the differences in percentage of total energy intake as simple CHO, complex CHO, proteins and fats between T2DM and non-T2DM groups. The percentage of T2DM participants adhering to diet plan and showing glycaemic controls were also examined. Results The mean (SD) of total calorie intake per day (Kcal) was 1547 (610, 95% CI 1486 to 1608) and 2132 (1892, 95% CI 1948 to 2316), respectively, for T2DM and non-T2DM groups. In the T2DM group (n=385), the mean (SD) percentage of total energy intake as total CHO, complex CHO and simple CHO was 64.1±8.3 (95% CI 63.3 to 64.9), 57.0±11.0 (95% CI 55.9 to 58.1) and 7.1±10.8 (95% CI 6.0 to 8.2), respectively. The mean (SD) percentage of complex CHO intake from total CHO was 89.5±15.3 (95% CI 88.0 to 91.1). The mean (SD) total protein/fat intake per day (g) was 57.1 (74.0)/37.2 (18.6) and 57.9 (27.2)/55.3 (98.2) in T2DM and non-T2DM groups, respectively. Conclusions Our study shows that CHO constitutes 64.1% of total energy from diet in T2DM participants, higher than that recommended in India. However, our findings need to be confirmed in a larger epidemiological survey. Trial registration number NCT01450592 & Clinical Trial Registry of India: CTRI/2012/02/002398.

Barriers and solutions to diabetes management: An Indian perspective.

India, with one of the largest and most diverse populations of people living with diabetes, experiences significant barriers in successful diabetes care. Limitations in appropriate and timely use of insulin impede the achievement of good glycemic control. The current article aims to identify solutions to barriers in the effective use of insulin therapy viz. its efficacy and safety, impact on convenience and life-style and lack of awareness and education. Therapeutic modalities, which avoid placing an undue burden on patients’ life-style, must be built. These should incorporate patient-centric paradigms of diabetes care, team-based approach for life-style modification and monitoring of patients’ adherence to therapy. To address the issues in efficacy and safety, long-acting, flat profile basal insulin, which mimics physiological insulin and show fewer hypoglycemic events is needed. In addition, therapy must be linked to monitoring of blood glucose to enable effective use of insulin therapy. In conjunction, wide-ranging efforts must be made to remove negative perception of insulin therapy in the community. Patient- and physician – targeted programs to enhance awareness in various aspects of diabetes care must be initiated across all levels of health-care ensuring uniformity of information. To successfully address the challenges in facing diabetes care, partnerships between various stakeholders in the care process must be explored.

Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India

Introduction: Zinc transporter-8 (ZnT8) is an islet cell secretory granule membrane protein recently identified as an autoantigen in type 1 diabetes (T1D). The aim of this study was to estimate the prevalence of antibodies to ZnT8 (ZnT8A) in juvenile onset T1D and to determine the utility of ZnT8A as an independent marker of autoimmunity either alone in antibody-negative subjects or in conjunction with glutamic acid decarboxylase (GAD) and insulinoma-2 antigen antibodies (GADA and IA2A). Research Design: ZnT8A, GADA, and IA2A were measured in sera of consecutive T1D patients (n = 88, age range 2-18 years) within 4 years of diagnosis and 88 sex-matched controls. Results: The prevalences of GADA, ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. IA2A were positive only in two patients who were negative for other two antibodies. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. In receiver operating characteristic (ROC) analysis, the performances of GADA and ZnT8As were better than that of IA2A; and AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59, respectively. Conclusions: ZnT8A complements GADA and increases the diagnostic sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of ZnT8A increases the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian T1D patients without loss of sensitivity and specificity.

Insulinoma case series: Experience of a tertiary care center.

Background: Insulinomas are usually solitary; benign and encapsulated small lesions and majority of them measure <2 cm in diameter. They pose a challenge for pre-operative localization. Definitive treatment is surgical excision of the tumor. Intra-operative ultrasonography (IOUS), transhepatic portal venous sampling (THPVS) and positron emission tomography (PET) scan can be done for tumors not localized by conventional imaging modalities. Materials and Methods: A retrospective study of patients diagnosed with insulinoma during the period 2004-2012 (8 years) was done. Biochemical diagnostic criteria used were plasma concentrations of glucose <55 mg/dl with corresponding insulin level >3.0 μU/ml (18 pmol/L) and C-peptide of >0.6 ng/ml (0.2 nmol/L). The localization of the tumor was done by various modalities namely computed tomography (CT), magnetic resonance imaging (MRI), IOUS, PET and portal venous sampling. The initial localizing technique in most of these patients were CT or MRI imaging, or both and those who were not localized by the above modalities were subjected to PET CT or THPVS or intra-operative ultrasound depending on the initial imaging results and patients consent. All the modalities were not used in the same patient, but the modalities were decided as per the imaging results, patients consent and affordability for the procedure. Results: Ninteen cases of insulinoma aged between 10 and 66 years, with a median age of 47 years were included in the analysis. There were 10 males and nine females. Eighty-three percent of patients presented with pre-prandial hypoglycemia (n = 15). Different modalities were employed for pre-operative localization of these patients out of which 5 (26.31%) cases were localized with CT, 5 (26.31) cases with MRI, 5 (26.31%) with THPVS, 1 (5.26%) case with PET CT, 3 (15.78%) of them could not be localized out of which 2 (10.52%) were localized by IOUS and 1 (5.26%) case the lesion could not be localized. Among 19 cases, 12 underwent surgery out of which one patient underwent distal pancreatectomy as tumor was not localized; eight underwent laparoscopic enucleation; three of them required intra-operative exploration and seven of them were not operated, as they did not give consent for surgery. In all the cases, the size of the insulinoma ranged between 1 and 2 cm. Conclusion: We report our experience with 19 cases of insulinoma and analyze the role of pre- and intra-operative imaging modalities in the surgical management of insulinomas. Most of our cases were symptomatic, and the most common presentation was with pre-prandial hypoglycemia. THPVS, PET scan and intra-operative ultrasound added to diagnostic sensitivity in some cases not localized by CT or MRI.

Oxidative Stress in Type 2 Diabetes with Iron Deficiency in Asian Indians

Oxidative Stress in Type 2 Diabetes with Iron Deficiency in Asian Indians A close relationship exists between iron metabolism, diabetes and oxidative stress. Both diabetes and redox active iron are individually known to enhance oxidative stress. However, the role of iron deficiency and oxidative stress in diabetes is not clear; hence, the levels of oxidative stress in type 2 diabetes with and without iron deficiency have been compared. Two groups of 30 patients each with diabetes were selected (one group with iron deficiency and the other group with normal iron levels) and compared with 30 normal healthy controls. The anthropometric parameters, fasting blood sugar, iron profile and oxidative stress parameters (malondialdehyde levels (index of lipid peroxidation) and serum uric acid levels (antioxidant)) were measured. While the diabetes group had significantly increased serum levels of ferritin (an acute phase reactant and antioxidant) in comparison with normal controls (P=0.040), the diabetic group with iron deficiency had decreased serum levels of iron (P =0.000), ferritin (P = 0.000) and uric acid (P = 0.006) and increased levels of malondialdehyde (P = 0.000) in comparison with diabetics without iron deficiency. This study shows an increase in oxidative stress in the diabetic group with iron deficiency together with reduction in antioxidant levels could further promote prooxidant levels and inflammation and in turn result in the development of complications in this high-risk Asian Indian population. Oksidativni Stres u Dijabetesu Tipa 2 sa Nedostatkom Gvožđa Kod Indijaca Metabolizam gvožđa, dijabetes i oksidativni stres blisko su povezani. Dijabetes i redoks-aktivno gvožđe zasebno pojačavaju oksidativni stres. Međutim, još nije ustanovljena uloga nedostatka gvožđa i oksidativnog stresa u dijabetesu; stoga su upoređeni nivoi oksidativnog stresa u dijabetesu tipa 2 sa i bez nedostatka gvožđa. Izabrane su dve grupe od po 30 pacijenata sa dijabetesom (jedna grupa sa nedostatkom gvožđa a druga sa normalnim nivoima gvožđa) i upoređene sa 30 zdravih kontrolnih subjekata. Izmereni su antropometrijski parametri, šećer u krvi na prazan stomak, profil gvožđa i parametri oksidativnog stresa (nivoi malondialdehida (indeks lipidne peroksidacije) i nivoi mokraćne kiseline u serumu (antioksidant)). Dok su u grupi dijabetičara nivoi feritina (reaktant akutne faze i antioksidant) u serumu bili značajno povišeni u poređenju sa zdravim kontrolnim subjektima (P = 0,040), u grupi dijabetičara s nedostatkom gvožđa bili su sniženi nivoi gvožđa (P = 0,000), feritina (P = 0,000) i mokraćne kiseline (P = 0,000) u serumu u poređenju s dijabetičarima bez nedostatka gvožđa. Ova studija pokazuje da bi porast oksidativnog stresa u grupi dijabetičara s nedostatkom gvožđa uz redukciju nivoa antioksidanata mogao dodatno povećati nivoe prooksidanata i pojačati inflamaciju, što bi za posledicu imalo razvoj komplikacija u ovoj visokorizičnoj indijskoj populaciji.

Spectrum of phenotype and genotype of congenital isolated hypogonadotropic hypogonadism in Asian Indians.

Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration and action. Although genetic aetiology of IHH is increasingly being studied, Asian Indian data on phenotypic spectrum and genetic basis are scarce.

Serum adiponectin levels in gestational diabetes mellitus

Introduction: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.[1] Pregnancy is a unique situation in which there is a physiological temporary increase in insulin resistance (IR). The mechanisms responsible for the gestational-induced IR are not completely understood. The current study was undertaken to compare adiponectin levels during 24–28 weeks period of gestation in drug-naive newly diagnosed GDM women with a cohort of normoglycemic pregnant women. Subjects and Methods: A total of 47 pregnant women in the age group of 18–40 years were included in this cross-sectional study, of which 13 were GDM cases and 34 were normoglycemic controls. Serum adiponectin level was analyzed by enzyme-linked immunosorbent assay. Results: The mean adiponectin level was 16.92 ng/ml (standard deviation [SD] = 2.78) and 19.38 ng/ml (SD = 2.71) in case and control groups, respectively, and the difference was found to be statistically significant (P = 0.008). Conclusion: Our study demonstrated decreased serum adiponectin levels in women with GDM when compared with age- and body mass index-matched euglycemic pregnant women.