49 Annual Conference of Endocrine Society of India, 21st -24th November 2019, Nagpur (ESICON 2019)

Take Home Message

Linagliptin causes significantly higher UACR reduction by 50% and 10% higher sustained UACR reduction >50%
GLP1/GIP/GCG triple co-agonist: Balanced GLP-1 and GIP activity to neutralize hyperglycemic risks of high GCG
T2D is a simple condition of fat excess and healthy people with active lifestyle can reverse T2D
Low carbohydrate ketogenic diet does admittedly shows dramatic improvement in short term but rarely sustainable
Calcium citrate maleate, calcium orotate, coral calcium and algae calcium are newer preparations of calcium
Various implications should be done such as obesogenic environment, reducing EI, voluntary reduction in EI, Pharmacotherapy, bariatric surgery

1. DPP‐4i Effects Beyond Glycemic Control

As per the Meslow based pyramid of diabetes the expextations of patients are changing from symptomatic well-being to comprehensive well-being
Patients need security, sufficiency and safety within the framework of sustainability
DPP-4i have simplified the management of diabetes by meeting the expectations of patients
DPP-4i have higher efficacy in Asian patients and among all the DPP-4is, Lingaliptin shows the greater efficacy
Unlike sulphonylureas, DPP-4i are not beta cell centric, rather they are islet centric as they have an effect on alphacells as well
Linagliptin is the only DPP-4i which does not need dose adjustment in any stage of renal impairment
Though all DPP-4i are similar in terms of efficacy, weight neutral, no hypoglycemia and tolerability; they are different in terms of PK/PD parametes, CV safety, heart failure and kidney safety
CAROLINA and CARMELINA trial provide evidence across broad spectrum of T2D duration, CV and kidney disease
Linagliptin shows no increased risk of HHF across high subgroups
Linagliptin causes significantly higher UACR reduction by 50% and 10% higher sustained UACR reduction >50%
Occurrence of hypoglycemia event is lower with Linagliptin compared to Glimepiride
DPP-4i can be used as a 2nd line agent st after Metformin, as 1st line if Meformin is rd contraindicated or not tolerated, as 3rd line after Metformin+SU, in patients where follow-up/monitoring/self-care is doubtful and in patients where co-morbid status is doubtful

2. GLP‐1 RA Recent Developments

GLP-1 RA are effective drugs for management of diabetes with potential advantages:
- Good efficacy in reducing HbA1c
- Minimal or no risk of hypoglycemia Weight reduction
- Pleiotropic benefit on brain, heart, kidney
- Potential for improved beta cell mass and function
Clinical disdavantges of GLP-1 RA includes gastrointestinal side effects, injectable and high cost
There are important differences between the different classes and the longer and oral GLP1 RAs are promising
GLP-1 has a vital role in weight loss
Targeting the glucagon: Glucagon receptor (GCGR) and glucagon receptor agonism
Gut hormone polyagonists for the treatment of T2D
GLP1/GIP/GCG triple co-agonist: Balanced GLP-1 and GIP activity to neutralize hyperglycemic risks of high GCG
Neuroprotective effects of GLP1, glucagon and GIP on Parkinson’s disease, Alzhemier’s disease, and Multiple sclerosis
Future of GLP1 RA in the form of incretin and gut hormone polyagonists for use in diabetes and obesity are bright

3. Reversal of Diabetes‐ Hype or Hope

Islets cells take up fat vividly, fat suppresses insulin secretion and increases apoptosis
Excess amount of food causes excess liver fat and increased hepatic glucose production
Bariatric surgery is known to cause a decrease in fasting plasma glucose in diabetes subjects
The hypothesis is that acute negative energy balance in people with T2D will normalise insulin sensitivity of the liver and restore the normal acute insulin response
In the COUNTERPOINT study, subjects were given very low calorie diet (VLCD) consisting of 600 kcal/day
- Beta cell function, liver and muscle insulin sensitivity and liver and pancreas fat were examined
- Body weight dropped by 3.9 kgs in subjects, beta cell function improved whereas there was no change in the muscle insulin sensitivity despite reversal of T2D
Twin cycle hypothesis is believed to be the etiology of T2D
The hypothesis predicted that there were metabolic vicious cycles operating in liver and pancreas, and that these should be able to be reversed
The primary driver of the metabolic problem was identified as positive energy balance, and reversing this was predicted to restore normal blood glucose control
Importantly, the hypothesis predicted that if the main driver of the twin cycles could be reversed, via negative calorie balance, then T2D could resolve in some, perhaps many, individuals
Hence, T2D is a simple condition of fat excess and healthy people with active lifestyle can reverse T2D

4. Ketodiet in Diabesity – Boon or Bane

Keto diet is a diet which is fundamentally a diet of 1920s, 1930s, 1940s and is still propagated
Keto diet is a diet which generates ketone bodies, causes ketosis and which has 30% cut in carbohydrates
Unhealthy lifestyle effectors including excessive calorie intake, unhealthy diet, sedentary lifestyle and mental stress modulate important metabolic and hormonal factors associated with development of most common chronic diseases
Diet quality impacts the metabolic risk through multiple pathways including altering energyintake, energy expenditure, microbiome host interaction, body fat composition and metabolic functions
Calorie restriction causes physiological adaption like improved endothelial function, lower blood pressure, lower heart rate, lower initma media thickness and lower left ventricular diastolic function thus preventing cardiovascular diseases
Evidence based dietary priorities for cardio-metabolic health have proven benefit of fruits, nuts, vegetable oils, whole grains, beans, yogurt etc. whereas unprocessed red meats, refined grains, starches, sugars, high sodium foods causes harm
Every stage of metabolic syndrome nutrition is the key
A meta-analyses of 23 trials was done comparing low carbohydrate diet containing less than or equal to 45% of carbohydrate versus low fat diet containing less than or equal to 30% of fat
- It was seen that both low carbohydrate and low fat diet improved weight and improved metabolic risk factors
Physiological ketosis occurs during fasting or exercise and nutritional ketosis is induced with nutritional and supplemental strategies
The metabolic state of ketosis should not be confused with ketoacidosis
A ketogenic diet consists of high fats, moderate protein and very low carbohydrate diet
- Dietary macronutrient is divided approximately 55 to 60% fats, 30 to 35% protein and 5 to 10% carbohydrates
- In a 2000 kcal diet, carbohydrate is upto 20 to 50 g of carbohydrate
Ketone bodies are nothing but glucose as an alternative fuel without hunger, burning fat for fuel that is ketones replace glucose as a primary source of energy
Standard keto diet consists of 70% fat, 20% protein and 10% carbohydrate
Cyclical is 5 days keto diet and 2 days high carb diet; targeted is standard keto diet with carbs surrounding workout; high protein keto diet is 60% fats, 35% protein and 5% carbs; fad diets is Atkins diet, modified Atkins diet and Paleo diet etc.
Lack of carbohydrate leads to depleted glycogen stores which prevent oxaloacetate from normal fat oxidation in Krebs cycle
After 3-4 days of fasting or low carbohydrate diet, our body enters ketosis and people experience brain fog or keto brain
Pros of keto diet include: better blood sugar control and weight loss, better blood profile, reduced blood pressure, increased HDL, very effective with greater adherence, increased satiety and increased leptin and insulin sensitivity
Difference between traditional and ketogenic diet is, in traditional diet cells use energy and in ketogenic diet, ketones enter the cells to produce energy
Although ketogenic diet has generated much attention for the dietary treatment of chronic diseases such as obesity and T2D, the evidence supporting its use is currently limited and diet’s potential risk is real
Low carbohydrate ketogenic diet does admittedly shows dramatic improvement in short term but rarely sustainable
Always advisable to be vigilant of the balance and interplay of nutrients and there should be a representation of all food groups on the plate
Moderation is the key should be used while following any long term diet plan

5. Calcium & Vitamin D Supplementation During Pregnancy

Endocrine society and Canadian guidelines recommend 2000 units of Vitamin D in pregnancy
Doses upto 4000 units have been found to be safe per day
When measured, target levels of 25 OH Vitamin D > 20 ng/ml
Higher doses are associated with better outcomes and better maternal vitamin D levels
Preparations of Vitamin D used in pregnancy are:
- Cholecalciferol: 2000 units daily or 60,000 units monthly
- Doses of upto 4000 U/day are safe in pregnancy
- Doses of upto 6000 U/day are safe in lactation
Calcitriol and Alfacalcidol is not to be used unless the subject has hypoparathyroidism
Studies recommend 1-2 gm of elemental calcium
Calcium carbonate-40% elemental calcium is well absorbed and welltolerated specially when taken with meal; it has limited solubility and abosrption in patients with high gastric pH
Calcium citrate-21% elemental calcium is better absorbed than CaCO in presence of 3 achlorhydria and it can be taken with or without food/H blockers/PPT
Calcium citrate maleate, calcium orotate, coral calcium and algae calcium are newer preparations of calcium
In pregnancy the total intake of calcium should be > 1000 mg/day (diet+tabs) and Vitamin D should be 2000 units/day
In lactation, the total intake of calcium should be > 1500 mg/day and Vitamin D should be 2000 units/day and in kids it should be 400 IU/day till first birthday

6. Endocrine Dysregulation in Obesity & Post Bariatric Surgery Management

In the weight maintenance, Energy intake should be equal to energy expenditure (EI=EE)
In the energy expenditure, 60-70% is BMR or RMR, 10% is Adaptive (BAT) and diet induced and 20% is NEAT (all spontaneous activity) and PE (Physical exercise)
The regulation of energy expenditure, BMR thermogenesis and activity are mainly considered
Adipocyte signal secrets leptin hormone which stimulate POMC neurons and inhibit NPY/AgRP neurons and leptin deficiency or resistance causes obesity
Gut signal secrets ghrelin hormone which is produced and absorbed when stomach is empty
Ghrelin secretagogue type 1A receptor (GHS-R1A) in hypothalamus
The hypothalamic regulation is generally exhibits in the arcuate nucleus, VMH and LH
POMC activation cause satiety and NPY activation causes feeding
The hormones such as ghrelin, GABA, beta endorphin, Galanin, CRH gives signals for feeding and leptin, GLP1, Oxyntomodulin, CCK, PYY from gut, serotonin, dopaminegives signal for satiety
Energy intake (EI) more than energy expenditure (EE) leads to weight gain and heritable factors regulate EE
Multiple signals from Gut/ adipocytes/ environment reach to hypothalamus
Homeostatic eating is regulated by endocrine system
Hedonic eating supersedes homeostatic regulation
There are various implications should be done such as obesogenic environment, reducing EI, voluntary reduction in EI, Pharmacotherapy, bariatric surgery