Take Home Message
- Maximum ratio of participants with adequate vitamin D levels may have reduced the study’s ability to detect an overall significance of vitamin D in the total study populations.
- The utility of the CNV Caller tool in recognising large-scale deletions causing MODY5, just as 17q12 deletion syndrome
- Atorvastatin treatment increased fasting and postprandial glucagon concentrations, which may indicate to hyperglucagonemia as a probable link between statin treatment and type 2 diabetes.
- Nutrition therapy suggestions need periodic adjustment and update, depending on the changes in an individual’s life circumstances, preferences, and disease course.
- Physicians need to overcome uncertainties about young patients and aggressively treat the youth battling T2D to minimize the damage from serious diabetes related complications.
- PREVIEW researchers estimated that the LCD followed by the standard dietary approach combined with either physical activity program would lead to a three-year incidence of T2D of 15.8%, and that the HP-LGI maintenance diet would reduce this incidence to 10.5%.
1. The Vitamin D and Type 2 Diabetes (D2d) Study-A Multicenter Randomized Controlled Trial for Diabetes Prevention
New research presented by Pittas AG on 7th JUNE 2019 at the American Diabetes Association (ADA) 79th scientific sessions in Moscone center, San Francisco, California. According to this research study, it shows that daily oral vitamin D supplementation does not effectively reduce the risk of type 2 diabetes among vitamin D-sufficient adults at high risk for developing the disease. D2d was designed to test whether 4000 IU per day of vitamin D3 (cholecalciferol) reduces the risk of diabetes among adults at high risk for diabetes, defined in the 2010 ADA guidelines as meeting at leasttwo of three glycemic criteria for prediabetes. A total of 2,423 participants were included which are at high risk for diabetes.Throughout the study period, participants were followed for new-onset diabetes with blood test every six months for a median of 2.5 years. The study was performed as an event-driven trial with a target total number of diabetes events of 508. This research study was designed to estimate a reduction in the risk of developing diabetes of 25%. Results from this study shows that vitamin D does not effectively reduce the risk of diabetes by the target level of 25% or more in the total study population. Fewer participants in the vitamin D group, 293 out of 1211 participants, 24.2%, developed diabetes as compared to placebo group, 323 out of 1212 participants, 26.7%, overall, insignificant reduction of 12% was reported. Maximum ratio of participants with adequate vitamin D levels may have reduced the study’s ability to detect an overall significance of vitamin D in the total study populations. It was concluded that in patients with high risk for type 2 diabetes and not selected for vitamin D insufficiency, vitamin D supplementation 3 at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo.
2. Simplifying Detection of Large Scale Deletions Causing MODY5
A was presented today 7 th June, 2019 at the American Diabetes Association (ADA) 79 th Scientific Sessions in Moscone center, San Francisco, California by Amanda J. Berberich. Maturity Onset Diabetes of the Young (MODY) 5, otherwise called renal cysts and diabetes syndrome, is an uncommon autosomal dominant form of monogenic diabetes caused by mutations in the HNF1B gene encoding hepatocyte nuclear factor 1 homeobox beta. Entire gene deletions of one copy of HNF1B are the most widely recognised mutation underlying MODY5, with more extensive deletions encompassing HNF1B and several surrounding genes, known as 17q12 deletion syndrome, present in a sub-set of individuals with MODY5, who present with additional clinical features. Verifiably, these huge scale deletions are not distinguished using Sanger or targeted next generation sequencing (NGS) panels, and needs other tools, for example, microarray-based genomic hybridization or multiplex ligation probe amplification to detect. Consolidating such tests to targeted sequencing adds essentially to cost and work. Ongoing advances in bioinformatics take into account distinguishing of large-scale copy number variation (CNV) from NGS output data without requiring additional laboratory methods.
The NGS information from 57 patients suspected to have MODY by their physicians however who were negative for pathogenic mutations using a targeted NGS approach were thus re-examined using a CNV calling tool (CNV Caller, VarSeq v1.4.3). Large scale deletions spanning HNF1B were seen in 3 patients. Whole exome sequencing data as well as microarray analysis (CytoScan, Affymetrix) were used to verify these deletions and they also confirmed the presence of 17q12 deletion in all three individuals. The deletions varied in size from 1.46 to 1.85 million base pairs. On evaluating further, a clinical correlation revealed a history of genitourinary abnormalities in all three probands. The authors concluded that these results confirm the utility of the CNV Caller tool in recognising large-scale deletions causing MODY5, just as 17q12 deletion syndrome. It also represents an easier, more financially savvy way to deal with making the diagnosis, at last improving case detection and taking into account more personalized care for affected individual.
3. The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males-A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?
A was presented today 7 th June, 2019 at the American Diabetes Association (ADA) 79 th Scientific Sessions in Moscone center, San Francisco, California by Martin L. Thomasen. Statins are LDL cholesterol-lowering drugs that are profoundly powerful in the prevention of cardiovascular disease and death. As of late, it has turned out to be realized that statin treatment expands the risk of type 2 diabetes, however the component behind this phenomenon stays darken. The authors conducted a study to evaluate the gluco-metabolic effects of statin therapy in healthy male individuals. A placebo-controlled, double-blinded, randomized, cross-over study was conducted to assess the effect of 14 days of treatment with atorvastatin (40 mg once-daily for one week and 80 mg once-daily the second week) on fasting and postprandial concentrations of glucose, gluco- regulatory hormones and bile acid profiles in 15 healthy male individuals (age 25.6±3.8 years; BMI 24.7±2.8 kg/m 2 ; glycated hemoglobin A1c 4.8±0.2% (mean±SD)). Four-hour mixed meal tests were performed following each of the two 14-day treatment periods with placebo or atorvastatin, respectively.
It was observed that the postprandial plasma glucose or insulin concentrations were not affected with atorvastatin, but basal and postprandial concentrations of glucagon were increased compared to placebo. Atorvastatin treatment increased the postprandial plasma concentrations of the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 as compared to placebo. In addition, an increase was seen in postprandial concentrations of taurine- conjugated primary bile acids and glycine-conjugated secondary bile acids decreased. It was observed that in healthy male individuals, 14 days of atorvastatin treatment did not influence postprandial glucose tolerance or insulin concentrations. Atorvastatin treatment increased fasting and postprandial glucagon concentrations, which may indicate to hyperglucagonemia as a probable link between statin treatment and type 2 diabetes.
4. Nutrition Counseling Improves Glycemic Targets, Achieves Weight Management Goals, and Improves Cardiovascular Risk Factors in Adults with Diabetes and Prediabetes
According to “The Nutrition Therapy for Adults with Diabetes or Prediabetes – A Consensus Report” study presented today at the American Diabetes Association’s (ADA’s) 79 th Scientific Sessions at the center in San Francisco, nutrition therapy increases glycemic control, improves weight loss, and provides beneficial results in cardiovascular outcomes. A medical nutrition therapy (MNT) is basic in the overall diabetes management plan, highlighted by American Diabetes Association (ADA) and the requirement for MNT should be reevaluated regularly by health care providers in co-operation with diabetic patients, with special attention during times of changing health status across the life span. Research gave clarity on many food choices and eating patterns that could aid people to gain health targets and quality of life. A search was performed on PubMed for studies between 1 January 2014 and 28 February 2018 published in English with the 2014 position statement was used as a starting point, to yield the upgraded evidence of nutrition therapy interventions in non-hospitalized adults with prediabetes and type 1 and type 2 diabetes.
It has been noticed that people with diabetes, eat about the same proportions of macronutrients, on average, as the general public: 45% of their calories from carbohydrate ;36– 40% of calories from fat, and the remainder (16–18%) from protein. An intensive lifestyle intervention resulting in weight loss could decrease the incidence of type 2 diabetes by 58% over 3 years in adults with overweight/ obesity and impaired glucose tolerance exhibited by Diabetes Prevention Program (DPP). Diabetic patients should eat at least the amount of fiber (minimum of 14 g of fiber per 1,000 kcal) with at least half of grain consumption suggested by the DGA 2015–2020. Mediterranean-style, low-fat, or low carbohydrate eating plans were the most robust research available associated to eating patterns for prediabetes or type 2 diabetes prevention. Also, participants who followed the very low-carbohydrate (VLC) eating pattern had spent more time in euglycemia and less time in hypoglycemia, showed less glycemic variability, and required less insulin. The SSBs replaced with an equal amount of water showed reduction in the risk of type 2 diabetes by 7–8%. Substantial decrease in both total cholesterol and LDL-C was seen by replacing saturated fat with unsaturated fats, decreases CVD risk. While a beneficial effect on blood pressure was perceived by reducing sodium to the general suggestion of 2,300 mg/day. It is imperative to maintain a balanced intake of food sources that lead to at least the proposed daily allowance for nutrients and micronutrients as necessary in people with diabetes. Patients not achieving glucose targets may show an elevated risk of micronutrient deficiencies. Nutrition therapy suggestions need periodic adjustment and update, depending on the changes in an individual’s life circumstances, preferences, and disease course. Further analyses and research on nutrition and eating patterns required in individuals with type 1 diabetes, type 2 diabetes, and prediabetes is needed.
5. Longitudinal Outcomes in Youth with Type 2 Diabetes-The TODAY2 Study
Much awaited results were presented today 8 th June, 2019 at the American Diabetes Association (ADA), 79 th Scientific Sessions in Moscone center, San Francisco, California by Zeitler P on The TODAY2 Study. The TODAY Study was the first multiethnic, multicenter, randomized trial examining youth-onset type 2 diabetes and remains unique in this category; comprising of racially and ethnically diverse participants with youth-onset type 2 diabetes who have been rigorously characterized and followed longitudinally since 2004 to better understand the clinical course of complications and comorbidities of youth-onset type 2 diabetes. As per results of TODAY, 45.6% of the cohort experienced treatment failure, with the highest rate being in the metformin monotherapy group, which was significantly higher than that of the metformin plus rosiglitazone group. The rate of failure for the metformin plus intensive lifestyle group was intermediate and was not different from either of the other groups. Participants from TODAY trial were invited to remain in TODAY2, which resulted in a cohort of 517 individuals with a current average age of 25 and diabetes duration of 12 years. The key objective of TODAY2 is to track the progression of type 2 diabetes and related comorbidities and complications as the participant's transition to young adulthood.
Findings from TODAY2 demonstrate the occurrence of major diabetes-related events in this young adult population, including heart attacks, chronic kidney disease, advanced diabetic retinal disease, early signs of diabetic nerve disease, and complications in offspring of pregnancies. Additional results of TODAY2 indicate that more than 60% had high blood pressure and more than 50% of the participants had abnormal lipid levels. On assessment, about 40% of participants have evidence for early diabetic disease and 50% have evidence for retina disease. Upto 33% of participants demonstrated early signs of diabetic nerve disease which was more common in those with worse glucose control. Out of 306 pregnancies reported by participants in TODAY2, 25% of the 2236 pregnancies with known outcomes resulted in miscarriage or fetal death and 24% in preterm births. Several risk factors and overt complications are not being aggressively managed as data from TODAY2 suggest. Physicians need to overcome uncertainties about young patients and aggressively treat the youth battling T2D to minimize the damage from serious diabetes related complications.
6. PREVIEW Study Results—Prevention of Diabetes through Lifestyle Intervention and Population Studies Around the World
Cumulative three-year incidence rate of type 2 diabetes drops to 4%, according to PREVIEW intervention study presented today at the ADA’s Scientific Sessions. PREVIEW is, to-date, the largest multi-national trial to address T2D prevention in adults with prediabetes through nutrition and exercise. Primarily, the study began in 2013 and enrolled 2,223 participants using intervention centers in Denmark, Finland, the United Kingdom, the Netherlands, Spain, Bulgaria, Australia, and New Zealand. The 36-month intervention consisted of two phases: a two-month period of rapid weight reduction achieved using an low-calorie diet (LCD) (800 kcal/day), followed by a 34-month randomized diet and exercise phase for weight loss maintenance consisting of four treatment arms. The impact of a high-protein, low-glycemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points were investigated. Screening was done on the basis of their Body Mass Index and other components of the Finnish Diabetes Risk Score. The study reported no difference between either of the post-weight loss diet or exercise-management programs, with the participants who had initially lost weight in all groups having a three-year incidence rate of T2D of 4%, which was much lower than anticipated. The primary hypothesis (based on the DiOGenes study) was a higher-protein (HP) diet with low glycemic index (LGI) carbohydrates combined with an initial period of weight loss would be more effective than a moderate protein and moderate glycemic index (GI) diet combined with an initial period of weight loss (based on the Finnish Diabetes Prevention Study and the Diabetes Prevention Program studies). The study also evaluated whether high-intensity, shorter duration physical activity was superior to moderate-intensity, longer duration physical activity.
PREVIEW researchers estimated that the LCD followed by the standard dietary approach combined with either physical activity program would lead to a three-year incidence of T2D of 15.8%, and that the HP-LGI maintenance diet would reduce this incidence to 10.5%. Of the 2,223 originally enrolled, 2,202 successfully lost 8% of weight during the LCD, and in January 2019 when the study ended, 962 still remained in the study at 36 months. The total number of cases of T2D was 62, giving a cumulative incidence rate of T2D of 4% over the three years. No differences were observed between the two diets or the two physical activity programs. Results of the international PREVIEW intervention study found that combining an initial low- calorie diet to establish significant weight loss followed by a maintenance diet and physical activity program with evidence-based advice on achieving behavioral change can achieve longer term maintenance of weight loss and reduce the risk of developing type 2 diabetes.
