Practice Update: Endocrinology

ADA 2016

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The ‘carbohydrate-first’ pattern showedmarked fluctuation in

SORELLA 1: SAR342434was as effective and well tolerated as insulin lispro in patients with type 1 diabetes. >12

Bariatric surgerywas shown to be associatedwith reduced longterm

postprandial glucose levels in contrast to very stable glucose levels with the ‘carbohydrate- last’ pattern. >11

incidence of complications affecting the eyes and kidneys both in patients with screen-detected and established type 2 diabetes. >10

Food order impacts postprandial glucose and insulin excursions significantly Food order has been found to exert a significant impact on postprandial glucose and insulin excursions and may be an effective strategy to attenuate postprandial glucose spikes and glycaemic variability in patients with type 2 diabetes. This conclusion, based on results of a follow-up study to a pilot trial

of a carbohydrate-last meal order. A lpana P. Shukla, MD, of Weill- Cornell Medical School, New York, explained that in a previous pilot study using a typical Western meal, she and colleagues demonstrated that in- gestion of protein and vegetables before carbohydrate leads to lower postprandial glucose and insulin excursions up to 120 minutes than eating carbohydrate first in a meal. “Standard nutritional counselling regarding carbohydrate consumption in diabetes,” Dr Shukla noted, “focuses on how much and what not to eat. Our previous pilot study suggested that the temporal sequence of carbohydrate con- sumption during a meal impacts glucose levels following a meal.” She continued, “In this follow-up study, we sought to validate those initial findings and gain further insight into the effect of food order on postprandial glycaemic response.” In this follow up study, the investiga- tors sought to examine the effect of food order on postprandial plasma glucose and insulin excursions in the setting of three commonly followed meal patterns with extended follow-up to 180 minutes, to capture delayed effects of food order on glycaemia. Seven overweight/obese subjects (body mass index 25–40 kg/m 2 ) with type 2 dia- betes (haemoglobin A 1c ≤ 8%) who were taking metformin were studied using a within-subject crossover design.

Compared to placebo, the area under the curve (0–240 minutes) for plasma glucose and insulin showed non-significant changes, while C-peptide was reduced more, by 27.2% with red grape cells vs placebo (P = 0.0409). As a result, estimated insulin sensitivity calculated from fasting glucose and C-peptide rose by 40.6% with red grape cells vs placebo (P < 0.0137). Postprandial mRNA expression of the clock genes showed non-significant changes in the transcription factors Bmal1 and Clock, while the repressor genes Per2, Cry1, and Rev-erb α , were significantly depressed (P < 0.05) with red grape cells vs placebo Dr Wainstein concluded that after 12-weeks of red grape cell supplementation in patients with type 2 diabetes, haemoglobin A 1c was improved, insulin sensitivity improved, and clock gene expression influenced significantly. Further study is needed to elucidate the best dosage and whether red grape cells might be useful as adjuvant therapy to achieve glycae- mic control in type 2 diabetes. “This issue needs further study,” she added, “with a larger sample size. The project is ongoing at our Centre. We are investigating the hormonal mechanisms underlying the effect of food order on glycaemia. Further research is also needed in larger numbers of patients with different meal patterns and meal compositions to assess the feasibility and effectiveness of this intervention across different populations.” insulin excursions. Food order may be an effective strategy to attenuate postpran- dial glucose spikes and glycaemic vari- ability in patients with type 2 diabetes, with implications for improving insulin sensitivity. “The ‘carbohydrate-first’ pattern,” she noted, “showed marked fluctuation in postprandial glucose levels in contrast to very stable glucose levels with the ‘carbohydrate- last’ pattern.” She continued, “This was clinically very relevant in that glycaemic variability is associated with increased risk of dia- betes- related complications. The insulin response was remarkable and suggests that the optimal food order (protein and vegetables first) may positively impact insulin sensitivity.” Dr Shukla asserted, “The effect of ini- tial carbohydrate consumption on post- meal glucose spikes was not significantly reduced when all meal components were consumed to together.”

After a 12-hour fast, subjects were ran- domly assigned to an isocaloric meal with the same composition on three separate days in one of the following food orders: 1.Carbohydrate(bread) followed 10 minutes later by protein (chicken) and vegetables 2. Protein and vegetables followed 10 minutes later by carbohydrate 3. All meal components eaten together as a sandwich Blood was sampled for measurement of glucose and insulin at baseline and at 30-minute intervals up to 180 minutes after the meal. Incremental areas under the curve for glucose (0–180) were similar, though the carbohydrate-first meal pattern demon- strated greater glycaemic variability with a higher peak at 60 minutes and lower nadir at 180 minutes. The average incremental glucose peak following ingestion of protein and vegetables first was 51% and 45% lower than eating carbohydrate first or eating all meal components together as a sand- wich, respectively. The incremental area under the curve 0–180 for plasma insulin was significantly lower when vegetables and protein were consumed first followed by carbohydrate vs other meal conditions. Dr Shukla concluded that food order has been found to exert a significant impact on postprandial glucose and

Red grape cell supplementation improves major parameters of type 2 diabetes Twelve weeks of red grape cell consumption by patients with type 2 diabetes has been shown to reduce haemo- globin A 1c , improve insulin sensitivity, influence clock gene expression significantly. J ulio Wainstein, MD, of E. Wolfson Medi- cal Centre, Tel Aviv, Israel, explained that disrupted clock genes mRNA expression Further study is needed to elucidate the best dosage and whether red

All patients underwent a meal test (520 kilo- calories, 29.4 g protein; 50.2 g carbohydrate; 44.7 g fat) at baseline and at the end of the study. After 12 weeks, greater reduction of hae- moglobin A 1c was observed for red grape cells, –0.55% ± 0.05% (from 7.85% ± 1.01% to 7.30% ± 0.75%, P = 0.0353) than for pla- cebo, –0.16% ± 0.15% (from 7.67% ± 0.55% was 29% greater with red grape cells than placebo. Within a subgroup with higher haemoglobin A 1c at baseline (7.5% to 10.1%), reduction of haemoglobin A 1c was –1.21% with red grape cells and –0.39% with placebo (P < 0.0247). to 7.51% ± 0.52%, not significant). Reduction of haemoglobin A 1c

in white blood cells is associated with type 2 diabetes. Resveratrol, a natural polyphenol, exerts potent modulatory effects on clock gene expression and has been linked to glycaemic regulation. The effects of red grape cells (a resveratrol polyphenol complex), on glycaemic control and clock gene (Bmal1, Clock, Per2, Cry1, and Rev-erb α ) mRNA expression have not been explored in type 2 diabetes. Dr Wainstein and colleagues set out to evaluate the impact of red grape cell sup- plementation on haemoglobin A 1c , plasma

glucose, insulin, C-peptide and clock gene mRNA expression in white blood cells. Thirty-three patients with type 2 diabetes age 63.7 ±7.1 years, body mass index 30.28 ± 4.58 kg/m 2 , and haemoglobin A 1c 7.76% ± 0.78% were randomised for 12 weeks to either supplementation with red grape cells 1000 mg daily or placebo. grape cells might be useful as adjuvant therapy to achieve glycaemic control in type 2 diabetes.

VOL. 1 • No. 1 • 2016