When are we Going to Settle the Diagnostic Criteria of Gestational Diabetes Mellitus?

Guidelines to diagnose Gestational Diabetes Mellitus (GDM) have changed a number of times from O'Sullivan and Mahan, Carpenter and Coustan, World Health Organization, American Diabetes Association to that of International Association of Diabetes in Pregnancy Study Group (IADPSG). The IADPSG guideline was based on Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study which was performed in caucasian population only and thus literally cannot be considered as international. Recently a study commented that this guideline needs revision for standardization of this strategy for diagnosing GDM. Based on a prospective study, Diabetes in Pregnancy Study Group India (DIPSI) recommended A single step procedure of diagnosing GDM with 2hr PG > 140 mg/dl after 75g of oral glucose administered irrespective of the last meal timing. This guideline has been approved by the Ministry of Health Government of India, WHO, IDF and Federation of Gynaecologists and Obstetricians Society (FIGO). National Institute of Clinical Excellence (NICE) also recognises cut off value, 2hr PG > 140 mg/dl based on a study in multi ethnic population of UK. Hence, we can safely conclude, A Single Step procedure has settled the criteria for diagnosing GDM.

Targeting Glycemic Level in Gestational Diabetes Mellitus to that of Normal Pregnancy would result in a better Maternal-Fetal Outcome.

ABSTRACT: Women with a history of Gestational Diabetes Mellitus (GDM) are at increased risk of future diabetes and related Non-Communicable Diseases (NCD) as are their offspring. "Transgenerational transmission occurs". Independent of genetic risk, offspring of hyperglycaemic pregnancies are at increased risk of early onset type 2 diabetes mellitus (Type 2 DM) and obesity. Differences exist in offspring risk of diabetes and obesity based on time and type of diabetes exposure in utero. There is a risk gradient, wherein type 2 DM exposure confers greater risk and reduces time to development of type 2 DM in the offspring compared with exposure to GDM and no diabetes exposure. These data suggest, glucose dose dependence in risk transmission. Given that the age of onset of prediabetes and type 2 DM is declining many reproductive age women may have undiagnosed diabetes or dysglycaemia when they become pregnant. This has great public health significance and it has become imperative that all pregnant women should be screened for hyperglycemia even if they have no symptoms. Ministry of Health, Government of India has developed the national guidelines for testing, diagnosis and management of hyperglycemia in pregnancy. These guidelines recommend early testing at booking, to be repeated again between 24-28 weeks if negative at first testing. The guideline also recommends that GDM can be diagnosed if the 2 hr PG is ≥140mg/dl after 75 gm of oral glucose administration without regard to the time of the last meal (i.e., fasting or non-fasting). This approach has also been endorsed by International Diabetes Federation (IDF), World Health Organization (WHO) and International Federation of Gynaecology and Obstetrics (FIGO) for resource constrained settings.The aim should be to target new born baby's birth weight, appropriate for gestational age (2.5 to 3.5 kg) to prevent the offspring developing NCD in the future. For this to happen early diagnosis and tight maternal glucose control during pregnancy similar to glycaemic level in the normal pregnancy, (FPG between 80 and 90 mg, 2 hr. post prandial between 110 and 120 mg) is necessary.

Use of Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitor Remogliflozin and Possibility of Acute Kidney Injury in Type-2 Diabetes.

The major trials, e.g., EMPA-REG OUTCOME, CANVAS, and CREDENCE, showed the renal and cardiovascular benefit of sodium-glucose transport protein 2 (SGLT2) inhibitors. The SGLT2 inhibitors, Empagliflozin, Dapagliflozin, and Canagliflozin, have shown no significant adverse renal effects. Still, our patients with type 2 diabetes on Remogliflozin, a type of SGLT2 inhibitor approved in India for the treatment of diabetes, seems to cause acute tubular necrosis as confirmed by clinical and pathological evidence in our study. The two critical findings in our research include a consistent rise in hs-CRP and a pathologist's biopsy report, excluding other causes. Therefore, we need sizeable cardiovascular-renal outcome trials to ascertain the safety of Remogliflozin in future studies.

Transgenerational Transmission of Non-communicable Diseases: How to Break the Vicious Cycle?

Non-communicable diseases (NCDs) like diabetes, obesity, hypertension, and cardiovascular diseases are major causes of morbidity and mortality all over the world. In recent decades, NCDs are sweeping steadily across the globe much like a silent yet devastating pandemic. Among other factors, the rising trend in diabetes and related NCDs is also linked to hyperglycemia in pregnancy (HIP). Maternal hyperglycemia acts as an in-utero insult to the developing fetus making the offspring prone to develop NCDs in adulthood. Resistance to the hormones insulin and leptin in the offspring affects the metabolic milieu predisposing the individual to obesity and diabetes. Epigenetic processes like DNA methylation, genomic imprinting, and histone modifications are likely to be impacted in an in-utero environment influenced by maternal hyperglycemia. HIP affects not only the health of the mother and her offspring but also sets up adverse intra-uterine programming that leads to a vicious cycle of transgenerational transmission of obesity, insulin resistance, diabetes, and other related NCDS to future generations. The need to break this vicious cycle is much essential now, more than ever before. Children, adolescents, and young adults should be encouraged to maintain a healthy weight and adopt a healthy lifestyle. Preconception counseling should begin early for women with diabetes, with continued guidance throughout their reproductive years. This article highlights how targeting pregnancy-related diabetes to break the chain of transgenerational transmission of NCDs would be an effective action to bring down the increasing burden of NCDs.

Diagnosis and principles of management of gestational diabetes mellitus in the prevailing COVID-19 pandemic.

BACKGROUND: Limited medical facilities are available due to Covid-19 pandemic. Nevertheless, all efforts should be made in planning judicial and possible methods of delivering health care, particularly to pregnant woman with GDM. GDM may play a crucial role in the increasing prevalence of diabetes and obesity and also may be the origin of cardiometabolic diseases. METHODS: It is mandatary to diagnose and care pregnant woman with GDM. The test suggested to diagnose GDM has to be evidence based and in this regard "a single test procedure" evaluated meets this requirement. This doable test has been accepted by the Diabetes in Pregnancy Study Group India (DIPSI) and approved by MHFW-GOI, WHO, International Diabetes Federation, and International Federation of Obstetricians and Gynecologists. MHFW-GOI also recommends testing at first antenatal visit and then at 24-28 weeks of gestation. This opportunity can also be utilized for performing ultrasonography for assessing fetal development. RESULT: The first-line management is MNT and life style modifications. Non-responders may require insulin or OHA. The target glycemic control is FPG ~ 5.0 mmol/dl (90 mg/dl) and 2 h PPPG ~ 6.7 mmol/dl (120 mg/dl). The goal is to obtain newborns birth weight appropriate for gestational age between 2.5 and 3.5 kg, a step to prevent offspring developing diabetes. CONCLUSION: The essential precaution required during COVID pandemic is to wear face mask, avoid crowded places, and maintain social distancing. Finally, the economical and evidence based "single test procedure" of DIPSI is most appropriate for screening during the COVID pandemic.

Perspectives on diagnostic strategies for hyperglycemia in pregnancy - Dealing with the barriers and challenges in South Asia.

Estimates indicate that south Asia accounts for over two fifths of the global burden of hyperglycemia in pregnancy (HIP) and the ongoing nutritional and epidemiological transition may make the situation worse. Given their higher risk, all women of south Asian decent require to be tested for HIP. With approximately 37 million births annually in the region requires that 37 million women be tested annually; thereby placing a huge burden on the fragile inadequately resourced health systems in the region with poor awareness and lack of trained manpower. Recommendation for testing must therefore be pragmatic, feasible, convenient and cost effective. Diabetes in pregnancy study group India (DIPSI) has proposed a simple testing protocol that is endorsed by the Indian National Guideline on GDM, and by the FIGO guideline on HIP for use in South Asia. This testing protocol has received widespread support in the region. Despite the many challenges it is encouraging to note that in the four large countries in the region - Bangladesh, India, Pakistan and Sri Lanka which account for over 80% of the estimated burden of HIP in south Asia, large scale credible programs have been initiated to address the identified barriers.

Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus.

PURPOSE: To investigate the long-term efficacy and safety of empagliflozin as add-on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. METHODS: Of 498 patients randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks in the EMPA-REG PIO™ study, 305 (61.2%) were treated in a double-blind extension trial for ≥52 weeks (total duration ≥76 weeks). Exploratory end points at week 76 included changes from baseline in glycosylated hemoglobin (HbA1c), weight, and blood pressure assessed using ANCOVA in patients who received ≥1 dose of study drug and had a baseline HbA1c measurement in the initial study. FINDINGS: Compared with placebo, adjusted mean (95% CI) changes from baseline in HbA1c level at week 76 were -0.59% (-0.79% to -0.40%; P < 0.001) for empagliflozin 10 mg (-6.5 [-8.6 to -4.4] mmol/mol) and -0.69% (-0.88% to -0.50%; P < 0.001) for empagliflozin 25 mg (-7.5 [-9.6 to -5.4] mmol/mol). Compared with placebo, adjusted mean (95% CI) changes from baseline in weight at week 76 were -2.0 kg (-2.7 to -1.2 kg; P < 0.001) and -1.7 kg (-2.4 -1.0 kg; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, only empagliflozin 25 mg led to significant reductions in systolic blood pressure (adjusted mean [95% CI] change: -3.7 mmHg [-6.1 to -1.3 mmHg]; P = 0.003) and diastolic blood pressure (adjusted mean [95% CI] change: -2.2 mmHg [-3.7 to -0.7 mmHg]; P = 0.004). Sensitivity analyses were consistent with these results for HbA1c level, fasting plasma glucose concentration, and weight, but revealed no significant difference between empagliflozin and placebo in change from baseline in systolic or diastolic blood pressure at week 76. Confirmed hypoglycemic adverse events (glucose ≤3.9 mmol/L and/or requiring assistance) were reported in 4.2%, 1.8%, and 3.0% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively; 1 patient each taking placebo and empagliflozin 25 mg required assistance. Adverse events consistent with urinary tract infection were reported in 26.7%, 22.4%, and 22.0% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Adverse events consistent with genital infection were reported in 3.0%, 10.3%, and 4.2% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. IMPLICATIONS: Empagliflozin 10 mg or 25 mg as add-on therapy to pioglitazone with or without metformin for 76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT01210001.

The cost-effectiveness of gestational diabetes screening including prevention of type 2 diabetes: application of a new model in India and Israel.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with elevated risks of perinatal complications and type 2 diabetes mellitus, and screening and intervention can reduce these risks. We quantified the cost, health impact and cost-effectiveness of GDM screening and intervention in India and Israel, settings with contrasting epidemiologic and cost environments. METHODS: We developed a decision-analysis tool (the GeDiForCE™) to assess cost-effectiveness. Using both local data and published estimates, we applied the model for a general medical facility in Chennai, India and for the largest HMO in Israel. We computed costs (discounted international dollars), averted disability-adjusted life years (DALYs) and net cost per DALY averted, compared with no GDM screening. RESULTS: The programme costs per 1000 pregnant women are $259,139 in India and $259,929 in Israel. Net costs, adjusted for averted disease, are $194,358 and $76,102, respectively. The cost per DALY averted is $1626 in India and $1830 in Israel. Sensitivity analysis findings range from $628 to $3681 per DALY averted in India and net savings of $72,420-8432 per DALY averted in Israel. CONCLUSION: GDM interventions are highly cost-effective in both Indian and Israeli settings, by World Health Organization standards. Noting large differences between these countries in GDM prevalence and costs, GDM intervention may be cost-effective in diverse settings.