Bruce R. King

Impact of Fat, Protein, and Glycemic Index on Postprandial Glucose Control in Type 1 Diabetes: Implications for Intensive Diabetes Management in the Continuous Glucose Monitoring Era

BACKGROUND Continuous glucose monitoring highlights the complexity of postprandial glucose patterns present in type 1 diabetes and points to the limitations of current approaches to mealtime insulin dosing based primarily on carbohydrate counting. METHODS A systematic review of all relevant biomedical databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, was conducted to identify research on the effects of dietary fat, protein, and glycemic index (GI) on acute postprandial glucose control in type 1 diabetes and prandial insulin dosing strategies for these dietary factors. RESULTS All studies examining the effect of fat (n = 7), protein (n = 7), and GI (n = 7) indicated that these dietary factors modify postprandial glycemia. Late postprandial hyperglycemia was the predominant effect of dietary fat; however, in some studies, glucose concentrations were reduced in the first 2–3 h, possibly due to delayed gastric emptying. Ten studies examining insulin bolus dose and delivery patterns required for high-fat and/or high-protein meals were identified. Because of methodological differences and limitations in experimental design, study findings were inconsistent regarding optimal bolus delivery pattern; however, the studies indicated that high-fat/protein meals require more insulin than lower-fat/protein meals with identical carbohydrate content. CONCLUSIONS These studies have important implications for clinical practice and patient education and point to the need for research focused on the development of new insulin dosing algorithms based on meal composition rather than on carbohydrate content alone.

Novel glucocorticoid and cAMP interactions on the CRH gene promoter.

Glucocorticoids inhibit corticotrophin releasing hormone (CRH) production in the hypothalamus but stimulate production from the placenta. We have sought to identify the key elements regulating the CRH gene. Mouse pituitary tumour-derived cells (AtT20 cells) were used in deletion and mutational analyses of the CRH promoter. Two cAMP responsive elements were identified: (I) a consensus cAMP response element (CRE) and (II) a previously unrecognised caudal-type homeobox response element (CDXRE). Glucocorticoids inhibit only the component of cAMP-stimulation occurring via the CRE through an action involving a negative glucocorticoid response element (nGRE). We also identified two regions that, in the absence of the nGRE, can be stimulated by glucocorticoids: (I) the CRE and (II) a region between -213 and -99 bps. Electrophoretic mobility shift assays (EMSAs) identified binding of the transcription factors CREB and Fos at the CRE in AtT20 cells while CREB and cJun were detected in placental cells. Tissue specific expression of transcription factors may mediate regulation of the CRH gene.

Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children With Type 1 Diabetes, and the Effect Is Additive

OBJECTIVE To determine the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT). RESEARCH DESIGN AND METHODS Thirty-three subjects aged 8–17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities: low fat (LF)/low protein (LP), LF/HP, HF/LP, and HF/HP. LF and HF meals contained 4 g and 35 g fat. LP and HP meals contained 5 g and 40 g protein. An individually standardized insulin dose was given for each meal. Postprandial glycemia was assessed by 5-h continuous glucose monitoring. RESULTS Compared with the LF/LP meal, mean glucose excursions were greater from 180 min after the LF/HP meal (2.4 mmol/L [95% CI 1.1–3.7] vs. 0.5 mmol/L [−0.8 to 1.8]; P = 0.02) and from 210 min after the HF/LP meal (1.8 mmol/L [0.3–3.2] vs. −0.5 mmol/L [−1.9 to 0.8]; P = 0.01). The HF/HP meal resulted in higher glucose excursions from 180 min to 300 min (P < 0.04) compared with all other meals. There was a reduction in the risk of hypoglycemia after the HP meals (odds ratio 0.16 [95% CI 0.06–0.41]; P < 0.001). CONCLUSIONS Meals high in protein or fat increase glucose excursions in youth using IIT from 3 h to 5 h postmeal. Protein and fat have an additive impact on the delayed postprandial glycemic rise. Protein had a protective effect on the development of hypoglycemia.

The regulation of human corticotrophin-releasing hormone gene expression in the placenta☆

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is expressed in the hypothalamus and the human placenta. Placental CRH production has been linked to the determination of gestational length in the human. Although encoded by a single copy gene, CRH expression in the placenta is regulated differently to the hypothalamus. Glucocorticoids stimulate CRH promoter activity in the placenta but inhibit its activity in the hypothalamus, via mechanisms involving different regions of the CRH promoter. We discuss how various stimuli alter CRH promoter activity and why these responses are unique to the placenta.

Can children with Type 1 diabetes and their caregivers estimate the carbohydrate content of meals and snacks

Diabet. Med. 27, 348–353 (2010)

Complex regulatory interactions control CRH gene expression.

Glucocorticoids inhibit corticotrophin releasing hormone (CRH) production in the hypothalamus but stimulate production from the placenta. To identify key elements regulating the CRH gene, mouse pituitary tumor-derived cells (AtT20 cells) were used as a hypothalamic model in an analysis of the CRH promoter. Two cAMP responsive elements were identified: (I) a consensus cAMP response element (CRE) and (II) a previously unrecognized caudal-type homeobox response element (CDXRE). Glucocorticoids inhibit only the component of cAMP-stimulation occurring via the CRE through an action involving a negative glucocorticoid response element (nGRE). We also identified two regions that, in the absence of the nGRE, can be stimulated by glucocorticoids: (I) the CRE and (II) a region between -213 to -99bps. Electrophoretic mobility shift assays identified binding of the transcription factors CREB and Fos at the CRE in AtT20 cells, whereas CREB and cJun were detected in placental cells. In addition, a novel CRE-binding transcription factor has been identified that is expressed in the brain and in placenta. A model is presented whereby CRH gene regulation is mediated via tissue specific expression of transcription factors.

Children and adolescents on intensive insulin therapy maintain postprandial glycaemic control without precise carbohydrate counting

Aims  Carbohydrate (CHO) quantification is used to adjust pre‐meal insulin in intensive insulin regimens. However, the precision in CHO quantification required to maintain postprandial glycaemic control is unknown. We determined the effect of a ±10‐g variation in CHO amount, with an individually calculated insulin dose for 60 g CHO, on postprandial glycaemic control.

A diabetes awareness campaign prevents diabetic ketoacidosis in children at their initial presentation with type 1 diabetes.

To evaluate the effect of a diabetes awareness campaign on the incidence of diabetic ketoacidosis (DKA) at the first presentation of type 1 diabetes in children (0–18 yr).

A randomized controlled trial of telephone calls to young patients with poorly controlled type 1 diabetes

Objective:  To determine if scheduled telephone calls from a pediatric diabetes educator to children who have type 1 diabetes improve hemoglobin A1c (HbA1c) level, hospital admissions, diabetes knowledge, compliance, and psychological well‐being.

Changes in Altitude Cause Unintended Insulin Delivery From Insulin Pumps: Mechanisms and implications

OBJECTIVE Children and adults with type 1 diabetes who receive insulin pump therapy have reported hypoglycemia during air travel. We studied the effects of atmospheric pressure on insulin pump delivery. RESEARCH DESIGN AND METHODS Ten insulin pumps were connected to capillary tubes. The effects of changes in ambient pressure on insulin delivery, bubble formation, bubble size, and cartridge plunger movement were analyzed. RESULTS During a flight (200 mmHg pressure decrease), excess insulin delivery of 0.623% of the cartridge volume occurred (P < 0.001, Student t test). In hypobaric chamber studies, bubbles developed in the insulin when the pressure decreased and displaced the insulin out of the cartridge. Pre-existing bubbles changed in size consistent with Boyle law. Cartridge plunger movement did not occur in normal flight conditions but did occur when catastrophic plane depressurization was mimicked. CONCLUSIONS Atmospheric pressure reduction causes predictable, unintended insulin delivery in pumps by bubble formation and expansion of existing bubbles.