Diabetes mellitus is a relentlessly evolving pandemic and a significant public health problem in recent decades. Diabetes disturbs millions of people worldwide, with a significant adverse effect on the quality of their lives. Efforts are underway worldwide to detect diabetes in its early stages and prevent complications of diabetes. Although in medical practice, what is accomplished by screening for hyperglycemia and detecting diabetes in the initial stages of its accepted history, recommends that impaired glucose tolerance is akin to the “primary prevention of diabetes.” Likewise, treating a patient with diabetes and handling those with diabetic problems are parallel to “secondary prevention” and “tertiary prevention,” respectively.

“Detection” of diabetes by screening does not mean “prevention.” What is needed is primordial prevention of diabetes; that is, the disease should not develop.

Diabetes Prevention Program in September 2001, the Centers for Disease Control and Prevention (CDC) issued a press release stating that “twin epidemics of diabetes and obesity continue to impend the health of Americans,” and the “Diabetes Prevention Program” was announced [1]. In 2001, 6.1% of the US population had been diagnosed with diabetes; currently, by 2021, about 10.5% of Americans have diabetes leading to a rethink of the goals of diabetes prevention programs. If this is not a successful program, what could be successful? Is it possible? To achieve diabetes-free generation whom to focus on? Lise Kingo suggested that female gender is the key to diabetes prevention. Based on the concept of developmental origin, the ovum is well supplied with mitochondria, but the sperm contains a few, and even those few do not persist in the offspring. At fertilization, only the spermatozoa’s nucleus enters the ovum; thus, all the cytoplasm, mitochondria, and mitochondrial DNA are exclusively maternally inherited [2].

Gestational programming is a process whereby stimuli, maternal fuels, or stresses that occur at critical or sensitive periods of fetal development permanently change structure, physiology, and metabolism, predisposing individuals to disease in adult life [3] -- “Fetal origin of adult diseases”. Detection of GDM is possible with 2-h PG > 140 mg/dl. The concern is about the prediction of GDM so that it can prevent the development of GDM and its consequences. Blood tests may identify gestational diabetes risk in the first trimester. NIH analysis suggests early screening could allow for lifestyle changes before the condition develops at the 10th week [5], which is possible if HBA1C is > 5.3% and the 2-h PPBS > 110 mg/dl.

NIH recommends screening at the 10th week as the fetal beta cell starts insulin secretion at the 11th week of gestation [4, 8]. Prandial glycemic level can be considered abnormal and may stimulate beta cell secretion.

Based on the Pattern of Glycemia in normal pregnancy [6] If:

  • PPBS at 10th week > 110 mg/dl predicts GDM; hence, blood glucose has to be brought to <110 mg/dl as fetal beta cells start secreting insulin around 10–11 weeks.

  • Then fetal insulin secretion leads to changes in maternal metabolism.

The obvious implication is that glycemic control needs to be optimized very early in pregnancy to prevent the establishment of fetal hyperinsulinemia [7]. Therefore, PPBS should be < 110 mg/dl.

Whenever maternal PPBS > 110 mg/dl is recorded, immediate action has to be taken to bring PPBS < 110 mg/dl, lest she will develop GDM and its consequences.

Fetal handling of maternal glucose (fetal hyperinsulinemia and maternal glucose) Fetal islet cells start secreting insulin from 11th week in response to maternal glucose. When the maternal glucose is high PPBS > 110 mg/dl, that time fetal hyperinsulinemia occurs and this will favor a persistently high glucose flux even at times when maternal glucose is normal. Maternal glucose does not go up due to fetal insulin handling maternal glucose which is deceptive. “Maternal hyperglycemia pushes glucose and fetal hyperinsulinism pulls glucose” and also disbursed fast in the fetal tissues and the glucose gradient is being maintained. The fetal glucose steal occurs through the placenta to the fetus. Hence, maternal hyperglycemia and fetal hyperinsulinemia promote fetal adiposity and result in male offspring obesity, IGT, and diabetes and in the female offspring result in obesity, GDM, and diabetes. Thus, the obvious implication is that glycemia control needs to be optimized early in pregnancy at 10th week PPBS < 110 mg/dl to prevent the establishment of fetal hyper-insularism. Fetal glucose steal is less highlighted in gestational diabetic pregnancies [9]. An exaggerated glucose steal by a hyperinsulinemia fetus could also attenuate maternal glucose levels during an oral glucose tolerance test (OGTT), elucidating why some mothers with affected fetuses have a normal glucose tolerance.

The idea is to test for glucose tolerance in the 8th week (2 months); the reason is prediction of GDM is 2-h PPBS > 110 mg/dl in the 10th week. Hence, in the 8th week itself, PPBS has to be estimated. If PPBS is > 110 mg/dl in the 8th week, a grace period of 2 weeks is available to attain PPBS < 110 mg/dl in the 10th week. If > 110 mg/dl, MNT and metformin 250 mg/bd must be started and continued [10]. The target glycemia to be obtained is PPBS 99 ± 10 mg/dl. Metformin is safe as the embryonic stage is over by the 8th week. To use metformin as an adjunct or alternative to insulin in the preconception period and during pregnancy, when the likely benefit from improved blood glucose control outweighs the potential for harm [11]. The study in The Lancet Diabetes & Endocrinology also showed no difference in weight, height, head circumference, and waist circumference between children of metformin-treated and placebo-treated mothers [12].

Preventive measures against NCD should start during the intrauterine period and continue throughout life from early childhood [13, 14]. Prevention of type 2 diabetes must begin in the uterus and continue throughout the life course.

The aim is to maintain maternal 2-h plasma glucose 99 ± 10 mg/dl throughout pregnancy from conception to confinement. This prevents the transgenerational transmission of diabetes.

Carry home message

  • Pre-pregnancy planning is ideal for a better fetal outcome.

  • It is necessary to optimize metabolic control early in pregnancy.

  • Prediction of GDM—PPBS > 110 mg/dl at 10th week.

  • Preventive action must be taken at the 8th week so maternal PPBS remains < 110 mg/dl throughout pregnancy.

  • MNT throughout pregnancy.

  • MNT + metformin to be continued till confinement.

The priming of the fetal beta cells around the 11th week with 2-h PPBS > 110 mg/dl may account for the persistence of fetal hyperinsulinemia throughout pregnancy.

  • This “Make in India” concept for primordial prevention of diabetes is evidence-based, feasible, and doable.

  • Hope to achieve diabetes-free generation.