bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Sitagliptin (SITA) Compared with Dapagliflozin (DAPA) in Subjects with T2D, Mild Renal Impairment, and Inadequate Glycemic Control on Metformin (MET) ± a Sulfonylurea (SU)
Authors: SCOTT RUSSELL S. , MORGAN JERRY D. , ZIMMER ZACHARY , LAM RAYMOND L.H. , O'NEILL EDWARD A. , KAUFMAN KEITH D. , ENGEL SAMUEL S. , RAJI ANNASWAMY 
Published: June 2018

While choice of AHAs may be modified in patients with T2D and moderate or severe renal insufficiency, this is generally not the case in patients with mild renal insufficiency. Clinical trial data focused on this population, which represents ∼40% of patients with T2D, are lacking.
In a randomized, double-blind, active comparator-controlled clinical trial, the safety and efficacy of adding SITA (100 mg qd) or DAPA (10 mg qd) to treatment of patients with eGFR ≥60 and &lt;90 mL/min/1.73 m2 and A1C ≥7.0% and ≤9.5% while on MET ± SU were assessed. The primary efficacy endpoint was change from baseline A1C at Week 24 (analyzed with a constrained longitudinal data analysis model), with a primary hypothesis of non-inferiority of SITA to DAPA based on the prespecified criterion of the upper bound of the between-treatment difference 95% CI (SITA minus DAPA) &lt;0.3%; if the upper bound was &lt;0.0%, SITA would be declared superior.
Treatment groups were well-balanced at baseline (n = 307 and 306, mean A1C [%] = 7.7 and 7.8, mean eGFR [mL/min/1.73 m2] = 79.4 and 76.9 for SITA and DAPA, respectively). At Week 24, LS mean changes from baseline A1C were -0.51% (SITA) and -0.36% (DAPA); between-group difference = -0.15%, 95% CI (-0.26, -0.04), p=0.006, confirming both non-inferiority and superiority of SITA vs. DAPA. The pre-specified analysis of 2 hour post-prandial glycemic excursion showed no significant difference between groups. The A1C goal of &lt;7% was met by 43% (SITA) and 27% (DAPA) of patients. Treatments were well tolerated; there were significantly fewer patients with drug-related adverse events (AEs) with SITA than with DAPA, but summary AE profiles were otherwise similar.
In summary, SITA treatment over 24 weeks resulted in greater glycemic efficacy and greater % of patients at A1C goal than DAPA in patients with T2D and mild renal impairment who were inadequately controlled on MET ± SU.

Disclosure
R.S. Scott: None. J.D. Morgan: Employee; Self; Merck & Co., Inc. Z. Zimmer: Employee; Self; Merck & Co., Inc. R.L.H. Lam: Employee; Self; Merck & Co., Inc. E.A. O'Neill: Employee; Self; Merck & Co., Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. A. Raji: Employee; Self; Merck & Co., Inc..
Efficacy and Safety of Sitagliptin (SITA)-Based Dual and Triple Combination Therapy in Older Chinese People with T2D
Authors: LIU XIANGYANG , WANG LI , XING YING , ENGEL SAMUEL S. , CHEN GUOJUAN , ZHANG YE , ZHANG RUYA , LIU SHU , WENG JIANPING , JI QIUHE 
Published: June 2018

Despite increasing prevalence of T2D in older Chinese people, no studies have evaluated the efficacy and safety of DPP-4 inhibitor-based combination therapy in this population. In the STRATEGY Study (a multicenter, randomized, active-controlled, open-label clinical trial in Chinese people with T2D), patients were treated for 20 weeks with a combination of SITA and metformin (MET) (Phase 1). Those with A1C ≥7.0% and ≤10.0% at Week 16 were randomly assigned at Week 20 to 1 of 4 additional AHAs and continued treatment for another 24 weeks (Phase 2). Here we report efficacy and safety in the 681 patients aged ≥65 year.
At baseline, the mean age, duration of diabetes, BMI and A1C of the analysis population were 68.4 year, 7.5 year, 25 kg/m2 and 7.7%, respectively; ≈half were male. Changes in A1C are shown in the Table. Achievement of A1C goal of &lt;7% was observed in 44.9% (305/680) during Phase 1, and 65.4% (445/680) during Phases 1 + 2.
Through Week 20/n=681 and Week 44/n=269, the incidences of any adverse events (AEs) were 30% and 31%, of drug-related AEs were 4% and 5%, and of serious AEs were 2% and 3%, respectively. Hypoglycemia incidences were highest with glimepiride and gliclazide (Table); no severe hypoglycemia was reported.
In older Chinese people, dual and triple combination therapy based on SITA and MET provided clinically meaningful improvement in glycemic control and was generally well tolerated.Phase 1 (Baseline through Week 20)Baseline A1C, mean ± SD, %Change from baseline A1C at Week 16, %Hypoglycemia, % (n/N) (APaT Population)SITA + MET, N = 6267.94 ± 0.78-0.81 ± 0.824.3% (29/681)Phase 2 (Weeks 20 through 44)Week 20 A1C, mean ± SD, %Change from Week 20 A1C at Week 44, %Hypoglycemia, % (n/n) (APaT Population)SITA + MET + glimepiride, n = 637.62 ± 0.82-0.73 ± 0.879.6% (7/73)SITA + MET + gliclazide, n = 697.68 ± 0.76-0.65 ± 0.7710.5% (8/76)SITA + MET + repaglinide, n = 477.69 ± 0.70-0.54 ± 0.785.9% (3/51)SITA + MET + acarbose, n = 647.59 ± 0.69-0.46 ± 0.731.5% (1/69)

Disclosure
X. Liu: None. L. Wang: None. Y. Xing: None. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. G. Chen: Employee; Self; Merck Sharp & Dohme Corp.. Y. Zhang: None. R. Zhang: Employee; Self; Merck Sharp & Dohme Corp.. S. Liu: None. J. Weng: None. Q. Ji: Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Medtronic. Research Support; Self; Merck & Co., Inc., Merck & Co., Inc..
Development of an Innovative Screening Tool and Identification of Novel ß-Cell Protective Drugs
Authors: SITHARA SMITHAMOL , PATEL BHAVISHA , ELLIS MEGAN K. , CROWLEY TAMSYN , WALDER KEN , ASTON-MOURNEY KATHRYN 
Published: June 2018

Type 2 diabetes (T2D) is characterised by progressive β-cell failure. While many drugs assist in the management of diabetes, current treatments cannot stop or slow the progression of this failure. In fact, over 50% of people with T2D have poor glycaemic control despite best practice management. Thus a key tool in T2D management would be the development of new drugs that restore adequate insulin secretion, but also protect against the continual deterioration of the β-cells. Previous drug discovery techniques have focused on single targets or pathways, however because β-cell dysfunction is extremely complex, targeting one pathway has proven to be ineffective. One approach that encompasses the intricacy of complex disease is that of gene expression signatures (GES) which have proved to be a valuable tool in other complex diseases.In this study, we developed a β -cell model consisting of three different conditions: 1) normal function/viability (“healthy”), 2) dysfunction/reduced viability (“diabetic”) and 3) successful treatment of dysfunction/reduced viability with a cocktail of known drugs (selected based on their ability to treat different aspects of β-cell dysfunction, “successfully treated”). We then used a comprehensive screening approach using gene expression profiles under these three conditions to generate a β-cell GES consisting of a gene set that robustly and accurately reflects the overall state of the cell. This GES was then used to screen a library of off-patent compounds, with known safety profiles, and the 12 top candidate compounds identified. In vitro testing of these drugs identified that nine significantly improved beta-cell function and survival. Therefore, we have developed a novel platform for T2D β-cell drug discovery and identified several candidate compounds that could prevent the progressive failure of β-cells. These drugs have the potential to be powerful T2D treatments and thereby reduce the burden of T2D and improve quality of life for millions world-wide.

Disclosure
S. Sithara: None. B. Patel: None. M.K. Ellis: None. T. Crowley: None. K. Walder: None. K. Aston-Mourney: None.
Development of Oral Bioavailable Nicotinamide N-Methyltransferase Inhibitors to Reduce Adiposity, Insulin Resistance, and Hyperglycemia
Authors: NEELAKANTAN HARSHINI , WATOWICH STAN 
Published: June 2018

There is a critical need for new mechanism-of-action drugs that reduce adiposity, a prime driver of type 2 diabetes. A novel target to treat adiposity and reverse type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in regulating adipose tissue metabolism and energy homeostasis. We have recently developed first-in-class small molecule NNMT inhibitors and characterized physicochemical, pharmacological, pharmacokinetic (PK), and off-target safety profiles of these inhibitors to identify a drug-like efficacious, orally bioavailable, and safe lead candidate for IND-enabling studies. Our first generation of highly selective, stable, and soluble compounds demonstrated excellent PK properties, including high oral bioavailability (&gt;90%) and half-life of 3 hours in rats. Finally, the efficacy of promising NNMT inhibitors at modulating adiposity and type 2 diabetes endpoints (e.g., fat mass, oral glucose tolerance, adipokine levels, circulating lipids) were assessed using diet-induced obese (DIO) mice maintained on a high-fat diet. Systemic treatment of DIO mice with a potent NNMT inhibitor significantly reduced body weight and white adipose tissue mass, decreased adipocyte cell size, and lowered plasma cholesterol levels (p&lt;0.05). Notably, administration of NNMT inhibitors did not alter total food intake nor produce any observable adverse effects. These results support continued development of small molecule NNMT inhibitors as therapeutics to lessen adiposity and lower the burden of adiposity-associated type 2 diabetes.

Disclosure
H. Neelakantan: None. S. Watowich: None.
Changes in Blood Glucose Levels and Body Weight in Patients Administered Sodium-Glucose Cotransporter 2 Inhibitors
Authors: KIM HUN-SUNG , LEE EUN YOUNG , YOON KUN-HO 
Published: June 2018

A few patients who are administered sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the first time often show an increase in their body weight and/or blood glucose levels. In this study, we used an electronic medical record database to identify the factors that affect blood glucose levels and body weight after the administration of SGLT2i. We investigated 1,663 patients who had been prescribed SGLT2i for the first time in a Korean hospital between December 2014 and December 2016. Based on the HbA1c levels measured 3 months following administration of SGLT2i, we observed that the blood glucose levels were significantly lowered in women or in elderly patients (all p &lt; 0.05). In patients who showed an estimated glomerular filtration rate (eGFR) ≥ 90 mg/dL (from 8.3% to 7.4%, p&lt;0.001) and those with an eGFR of 60-90 mg/dL (from 7.9% to 7.2%, p&lt;0.001), the HbA1c was observed to demonstrate a significant drop. However, in patients with an eGFR ≤ 60 mg/dL, the HbA1c tended to demonstrate a marginal rise slightly (from 8.1% to 8.5%, p&lt;0.001). A similar pattern of changes was observed with regard to patients’ weight. Significant weight loss and improvement in blood glucose levels were observed in those with a baseline HbA1c level ≥ 9.0%. However, the weight loss observed was relatively less significant in those with a baseline HbA1c level of 7.0-8.0% and 8.0-9.0%. We conclude that the reduction in blood glucose levels and the weight loss induced by SGLT2i appear to be strongly influenced by/associated with gender, age, and eGFR. While large-scale clinical studies are needed in the future, it seems worthwhile to check the clinical condition of SGLT2i-prescribed patients in advance and expect changes in weight and blood sugar reduction. Although large-scale clinical studies are needed in the future to conclusively corroborate our results, it is recommended that patients administered SGLT2i be monitored closely for weight changes and improvements in blood sugar levels.

Disclosure
H. Kim: None. E. Lee: None. K. Yoon: None.
Maternal Type 1 Diabetes and Risk of Autism in Offspring
Authors: XIANG ANNY , WANG XINHUI , MARTINEZ MAYRA P. , PAGE KATHLEEN A. , BUCHANAN THOMAS A. 
Published: June 2018

Children exposed in utero to maternal type 2 diabetes (T2D) or gestational diabetes (GDM) diagnosed by 26 weeks gestation are at increased risk of autism spectrum disorders (ASD). Here we assessed the association between ASD and in utero exposure to maternal type 1 diabetes (T1D). Data were from 419,425 singleton children born at 28-44 weeks’ gestation from 1995-2012 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC membership, death due to any cause, or December 31, 2016. Relative risks of ASD were estimated by hazard ratio (HR) using Cox regression models adjusted for birth year, maternal age, parity, education, household income, race/ethnicity, history of comorbidity, and sex of the child. A total of 621 children were exposed to T1D, 9,453 to T2D, 11,922 to GDM diagnosed by 26 weeks gestation, and 24,5to GDM diagnosed after 26 weeks gestation. During a median of 6.3 (interquartile range of 3.4-11.2) years after birth, 5,624 children were diagnosed with ASD (19 exposed to T1D, 221 to T2D, 250 to GDM by 26 weeks, 360 to GDM after 26 weeks, and 4,774 not exposed to maternal diabetes). Unadjusted annual ASD incidence rates per 1000 children were 4.7 (T1D), 3.7 (T2D), 3.1 GDM by 26 weeks, 2.2 (GDM after 26 weeks) and 1.9 (unexposed). Relative to no diabetes exposure, the adjusted HRs for exposure to maternal diabetes were 2.5 (95% CI, 1.4-4.4) for T1D, 1.5 (95% CI, 1.3-1.7) for T2D, 1.4 (95% CI, 1.2-1.6) for GDM by 26 weeks, and 1.0 (95% CI, 0.9-1.1) for GDM after 26 weeks gestation respectively. Thus, exposures to T1D, T2D and GDM diagnosed by 26 weeks gestation were all associated with an increased risk of autism spectrum disorders in offspring. Exposure to T1D imparted the highest risk, followed by exposure to T2D and GDM diagnosed by 26 weeks. Rising rates of maternal diabetes may be one factor contributing to rising rates of ASD.

Disclosure
A. Xiang: None. X. Wang: None. M.P. Martinez: None. K.A. Page: None. T.A. Buchanan: None.
Dapagliflozin plus Saxagliptin Add-On to Metformin Reduces Liver Fat and Adipose Tissue Volume in Patients with Type 2 Diabetes
Authors: WILDING JOHN P. , HOCKINGS PAUL , JOHNSSON EVA K. , MAASKE JILL , GARCIA-SANCHEZ RICARDO , JOHANSSON LARS 
Published: June 2018

Oral administration of a fixed-dose combination of the SGLT2 inhibitor dapagliflozin (DAPA) and the DPP-4 inhibitor saxagliptin (SAXA) is approved for improving glycemic control in adult patients with type 2 diabetes (T2D). A 52-week, multicenter, randomized, double-blind, parallel-group trial (NCT02419612) evaluated the efficacy and safety of DAPA 10 mg/d + SAXA 5 mg/d vs. titrated glimepiride (GLIM) 1-6 mg/d in 443 patients with T2D (A1C 7.5-10.5%) on metformin (MET) ≥1500 mg/d background. In a substudy, we used magnetic resonance imaging (MRI) to assess effects on liver fat (proton density fat fraction [PDFF]) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment. MRI was performed on 59 patients; liver fat and adipose tissue volumes were analyzed for 59 and 57 patients, respectively. There was a significant &gt;30% reduction from baseline in liver fat (P=0.007) and a &gt;10% reduction in adipose tissue volumes (P&lt;0.01) with DAPA + SAXA + MET at week 52 vs. GLIM + MET (Table). In the full study population, DAPA + SAXA + MET decreased body weight and serum levels of alanine aminotransferase and aspartate aminotransferase over 52 weeks.
In conclusion, DAPA + SAXA significantly decreased liver fat and adipose tissue volume vs. GLIM, and reduced serum liver enzyme levels, indicating a favorable metabolic profile of DAPA + SAXA in patients with T2D on MET therapy.

Disclosure
J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck & Co., Inc. P. Hockings: Other Relationship; Self; MedImmune, AstraZeneca. E.K. Johnsson: Employee; Self; AstraZeneca. J. Maaske: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. Stock/Shareholder; Spouse/Partner; AstraZeneca. R. Garcia-Sanchez: Employee; Self; AstraZeneca. L. Johansson: Stock/Shareholder; Self; Antaros Medical.
Canagliflozin Improves a Left Ventricular Diastolic Dysfunction without Affecting Baroreflex Sensitivity in Type 2 Diabetes
Authors: MATSUTANI DAISUKE , SAKAMOTO MASAYA , KAYAMA YOSUKE , UTSUNOMIYA KAZUNORI 
Published: June 2018

In type 2 diabetes, there is no effective treatment for gradual progression of left ventricular (LV) diastolic dysfunction and reduced baroreflex sensitivity (BRS), which is a sensitive measure of cardiovascular (CV) autonomic function. Here we prospectively evaluated the effect of Canagliflozin, sodium-glucose cotransporter (SGLT) 2 inhibitor, on LV diastolic dysfunction and BRS at the same time. 37 type 2 diabetic patients with high risks of CV disease were enrolled. All participants were evaluated LV function, BRS, HbA1c, Hb, BNP and t-PA-PAI-1 complex before and after 3 months of the additional treatment with Canagliflozin. Multiple-linear regression was used to assess individual and cumulative effects of δearly diastolic velocity/basal septal diastolic velocity (E/e’) and δLV mass index. UMIN000025964 for Clinical Trials Registry. Characteristics of the subjects are age 64.2 ± 8.1 years (mean±SD), HbA1c 7.9±0.7%, diabetes duration 13.5 ± 8.1 years, complicated CV disease 32.4%. E/e’ ratio (13.7 ± 3.5 to 12.1 ± 2.8, p = 0.001), LV mass index (82.0 ± 15.8 to 77.3 ± 16.4 g/m2, p = 0.003), HbA1c (7.9 ± 0.7 to 7.1 ± 0.6%, p = 0.000), and t-PA-PAI-1 complex (27.0 ± 15.8 to 19.4 ± 7.0 ng/mL, p =0.002) were decreased and Hb (13.9 ± 1.2 to 14.7 ± 1.4 g/dL, p =0.000) was increased. The level of BRS (10.7 ± 8.5 to 10.2 ± 7.3 msec/mmHg, p = 0.721) and BNP (15.1 ± 10.7 to 13.5 ± 10.1 pg/dL, p = 0.062) did not show any differences. Interestingly, δE/e` were negatively correlated with baseline E/e` and δHb (r=-0.618, p=0.000; r=-0.496, p=0.002, respectively). Multiple regression model still revealed that δE/e` were related to baseline E/e` (β=-0.581, p=0.007) and δHb (β=-0.406, p=0.009) independently of age, sex, and baseline SBP (R-squared 0.469). Canagliflozin improved LV diastolic dysfunction without reducing BRS in type 2 diabetic patients with high CV disease risk. Our results suggest that greater increase of Hb is a surrogate marker of improvement of diastolic function.

Disclosure
D. Matsutani: None. M. Sakamoto: None. Y. Kayama: None. K. Utsunomiya: None.
Enteral Insulin Attenuates Fatty Liver Signs and Symptoms in Mice on a High-Fat Diet
Authors: SAFADI RIFAAT , SALHAB AHMAD , AMER JOHNNY , WEISS DANIEL J. , BLUMENFELD DANIELA , MINTZ YOAV , KUNICHER NIKOLAI , KIDRON MIRIAM 
Published: June 2018

Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disorder in the USA, affecting 90% of morbidly obese individuals and often clustering with prediabetes or overt type 2 diabetes mellitus. While its exact pathogenesis remains unclear, insulin resistance and obesity are considered contributing and risk factors, suggesting effective blood glucose control as a means of preventing and managing NAFLD. To assess this treatment avenue, C57b1/6J mice maintained on a high-fat diet (HFD) for 13 weeks, were treated daily with insulin (INS; 3.6 mg/kg), delivered via a feeding tube, or sham-saline treatment for three consecutive weeks. Peripheral blood and liver samples were collected to analyze inflammatory and fibrosis markers and to histologically assess NAFLD activity score (NAS). Following the treatment period, INS HFD mice demonstrated lower body weight (8.6±1.8 g vs. 7.5±4.1 g) and significantly lower NAS (0.11 vs. 3.7; p&lt;0.005) as compared to sham HFD mice. Further, the mean baseline alanine aminotransferase (ALT) levels of 212±223.6 U/L dropped to 38.3±34.5 U/L and 88.4±85.3 U/L in sham and INS animals, respectively. However, post-treatment aspartate aminotransferase (AST) levels were unchanged in sham HFD animals (202.8±83.7 U/L), but were two-fold lower in INS mice (123.2±80.4 U/L; p=0.03). Mean AST/ALT ratios, a reliable indicator of liver disease, were significantly lower among INS, as compared to sham mice (2.6±1.3 vs. 4.7±2.9; p=0.04). Change from baseline alpha smooth muscle actin (αSMA) RNA levels, a hallmark of fibrosis, was lowest among INS (0.31±0.23-fold increase) as compared to saline-treated HFD mice (0.58±0.14). In parallel, a consistently higher percentage of active, antifibrotic (NKP46+) CD3+ natural killer cells were observed among INS vs. sham and untreated NFD mice. These preliminary findings provide a proof of concept for the potentially therapeutic effect of enteral insulin on fibrotic and inflammatory processes in the liver.

Disclosure
R. Safadi: None. A. Salhab: None. J. Amer: None. D.J. Weiss: None. D. Blumenfeld: None. Y. Mintz: None. N. Kunicher: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals, Inc..
Pregnancy Glycemia Reflects Life Course Glycemia of the Mother
Authors: MEMANE NILAM S. , BHAT DATTATRAY , RAUT DEEPA A. , BONDARDE SOMNATH J. , LADKAT RASIKA , YAJNIK PALLAVI C. , FALL CAROLINE , YAJNIK CHITTARANJAN S. 
Published: June 2018

Background: Current practice of diagnosis and treatment of GDM is largely restricted to late pregnancy, ignoring peri-conceptional window which is crucial for fetal programming of diabetes. A few longitudinal studies reported that metabolic risk factors of GDM are present before pregnancy but there are no reports on a ‘lifecourse’ trajectory of pregnancy glucose insulin metabolism. Pune Maternal Nutrition Study (PMNS) offers a unique opportunity to investigate the association between gestational glycaemia and pre-pregnancy lifecourse glycaemia because of serial measurements from childhood to pregnancy.
Methods: We studied 328 female offspring of PMNS born in 1993-96 for glucose insulin measurements at 6, 12, and 18 year of age. Girls who became pregnant underwent a 75 gm OGTT at 28 weeks gestation. We studied the association between gestational fasting plasma glucose (FPG) with their earlier measurements using multiple linear regression analysis.
Results: Up to October 2017, 110 women had an OGTT at 28 weeks gestation and have delivered. Thirteen (11.8%) were diagnosed GDM (IADPSG criteria 2011) In lifecourse analysis, FPG tracked from 6 years of age to pregnancy through 12 and 18 years. FPG at 28 weeks was directly associated with her own FPG at 18, 12 and 6 years of age (β= ∼0.3, p&lt;0.001), and it was inversely associated with disposition index at 18 and 12 years (p&lt;0.05).
Conclusions: The world’s first description of lifecourse evolution of pregnancy glycaemia suggests that it tracks from early childhood and is associated with impaired beta cell function. The analysis provides an important clue that GDM women have higher pre and peri-conceptional glycaemia which is a risk factor for fetal programming of diabetes. Current clinical approach to GDM ignores this important window. This could be a potential explanation of the failure of current practice of GDM treatment in late pregnancy to reduce long term risks in the offspring.

Disclosure
N.S. Memane: None. D. Bhat: None. D.A. Raut: None. S.J. Bondarde: None. R. Ladkat: None. P.C. Yajnik: None. C. Fall: None. C.S. Yajnik: None.