The Benefits and Limits of Technological Advances in Glucose Management Around Physical Activity in Patients Type 1 Diabetes

Physical activity is highly recommended for patients living with type 1 diabetes (T1D) due to its varied health benefits. Nevertheless, glucose management, during and in the hours following exercise, represents a great challenge for these patients who most often end up leading a sedentary life style. Important technological advances in insulin delivery devices and glucose monitoring are now available and continue to progress. These technologies could be used to alleviate glucose management related to physical activity in T1D. Continuous glucose monitoring (CGM) helps patients observe the trends of glycemic fluctuations when exercising and in the following night to deal pre-emptively with hypoglycemic risks and treat hypoglycemic episodes in a timely manner. Insulin pumps offer the flexibility of adjusting insulin basal rates and boluses according to patient's specific needs around exercise. The artificial pancreas links CGM to pump through an intelligent hormone dosing algorithm to close the loop of glucose control and has thus the potential to ease the burden of exercise in T1D. This review will examine and discuss the literature related to physical activity practice using each of these technologies. The aim is to discuss their benefits as well as their limitations and finally the additional research needed in the future to optimize their use in T1D

The potential causes of cystic fibrosis-related diabetes

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity, affecting more than 50% of adult CF patients. Despite this high prevalence, the etiology of CFRD remains incompletely understood. Studies in young CF children show pancreatic islet disorganization, abnormal glucose tolerance, and delayed first-phase insulin secretion suggesting that islet dysfunction is an early feature of CF. Since insulin-producing pancreatic β-cells express very low levels of CFTR, CFRD likely results from β-cell extrinsic factors. In the vicinity of β-cells, CFTR is expressed in both the exocrine pancreas and the immune system. In the exocrine pancreas, CFTR mutations lead to the obstruction of the pancreatic ductal canal, inflammation, and immune cell infiltration, ultimately causing the destruction of the exocrine pancreas and remodeling of islets. Both inflammation and ductal cells have a direct effect on insulin secretion and could participate in CFRD development. CFTR mutations are also associated with inflammatory responses and excessive cytokine production by various immune cells, which infiltrate the pancreas and exert a negative impact on insulin secretion, causing dysregulation of glucose homeostasis in CF adults. In addition, the function of macrophages in shaping pancreatic islet development may be impaired by CFTR mutations, further contributing to the pancreatic islet structural defects as well as impaired first-phase insulin secretion observed in very young children. This review discusses the different factors that may contribute to CFRD

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges

AimsNon-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15–20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges.MethodsThis is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0–3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at 45 min post-initial treatment. Subcutaneous insulin was used in a fasting state to induce NS-H. Participants had frequent venous sampling of PG, insulin, and glucagon levels.ResultsParticipants (n = 32; 56% female participants) had a mean (SD) age of 46.1 (17.1) years, had HbA1c at 54.0 (6.8 mmol/mol) [7.1% (0.9%)], and had a diabetes duration of 27.5 (17.0) years; 56% were insulin pump users. We compared NS-H correction parameters between 16 g and 32 g of CHO for range A, 3.0–3.5 mmol/L (n = 32), and range B, <3.0 mmol/L (n = 29). Change in PG at 15 min for A: 0.1 (0.8) mmol/L vs. 0.6 (0.9) mmol/L, p = 0.02; and for B: 0.8 (0.9) mmol/L vs. 0.8 (1.0) mmol/L, p = 1.0. Percentage of participants with corrected episodes at 15 min: (A) 19% vs. 47%, p = 0.09; (B) 21% vs. 24%, p = 1.0. A second treatment was necessary in (A) 50% vs. 15% of participants, p = 0.001; (B) 45% vs. 34% of participants, p = 0.37. No statistically significant differences in insulin and glucagon parameters were observed.ConclusionsNS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0–3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption.Clinical trial registrationClinicalTrials.gov, identifier NCT03489967

CFTR Depletion Results in Changes in Fatty Acid Composition and Promotes Lipogenesis in Intestinal Caco 2/15 Cells

Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The mechanism(s) underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role.The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7)/16:0, was significantly higher in knockdown cells and consistent with the striking elevation of the n-7 FA family. When incubated with [14C]-oleic acid, CFTR-depleted cells were capable of quick incorporation and export to the medium concomitantly with the high protein expression of L-FABP known to promote intracellular FA trafficking. Accordingly, lipoprotein vehicles (CM, VLDL, LDL and HDL), isolated from CFTR knockdown cells, exhibited higher levels of radiolabeled FA. Moreover, in the presence of [14C]-acetate, knockdown cells exhibited enhanced secretion of newly synthesized phospholipids, triglycerides, cholesteryl esters and free FA, thereby suggesting a stimulation of the lipogenic pathway. Conformably, gene expression of SREBP-1c, a key lipogenic transcription factor, was increased while protein expression of the phosphorylated and inactive form of acetylCoA carboxylase was reduced, confirming lipogenesis induction. Finally, CFTR-depleted cells exhibited lower gene expression of transcription factors (PPARalpha, LXRalpha, LXRbeta and RXRalpha).Collectively, our results indicate that CFTR depletion may disrupt FA homeostasis in intestinal cells through alterations in FA uptake and transport combined with stimulation of lipogenesis that occurs by an LXR/RXR-independent mechanism. These findings exclude a contributing role of CFTR in CF-associated fat malabsorption

Barriers to Physical Activity Among Patients With Type 1 Diabetes

OBJECTIVE—To determine, in an adult population with type 1 diabetes, barriers to regular physical activity using a diabetes-specific barriers measure (the Barriers to Physical Activity in Diabetes [type 1] [BAPAD1] scale) and factors associated with these barriers

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF

Morning hyperglycemic excursions. A constant failure in the metabolic control of non-insulin-using patients with type 2 diabetes

WSTĘP. Celem pracy było ustalenie występowania w ciągu dnia epizodów hiperglikemii prowadzących do złej kontroli metabolicznej u chorych na cukrzycę typu 2. MATERIAŁ I METODY. Badana grupa liczyła 200 chorych na cukrzycę typu 2 leczonych lekami doustnymi i/lub dietą. W populacji tej badano profile dobowe glikemii i insulinemii. Pomiarów stężenia glukozy dokonywano na czczo bezpośrednio przed śniadaniem o 8.00 rano, następnie w okresie poposiłkowym o godz. 11.00 i 14.00) oraz w okresie poabsorpcyjnym o 17.00. WYNIKI. W całej populacji wartości glikemii przed obiadem (12,0 mmol/l) były znamiennie podwyższone (p < 0,0001) w porównaniu z glikemią mierzoną o godzinie 8.00 (8,8 mmol/l), 14.00 (10,5 mmol/l) i 17.00 (8,6 mmol/l). Podobny wzrost glikemii przedobiedniej (p < 0,0001) obserwowano w grupach chorych dobranych według kryteriów: 1) masy ciała; 2) wieku; 3) HbA1c; 4) sposobu leczenia; 5) rezydualnej funkcji komórek b. Z obliczeń pól pod krzywą dziennego przebiegu glikemii wynika, że w całkowitym podwyższeniu stężenia glukozy w surowicy względny udział glikemii na czczo i poposiłkowej jest zbliżony. WNIOSKI. Wysokie stężenia glukozy w surowicy w okresie przedpołudniowym są dość charakterystycznym wykładnikiem niepowodzenia leczenia cukrzycy typu 2 z zastosowaniem diety i leków doustnych. Hiperglikemie przedobiednie występują niezależnie od cech klinicznych (wskaźnik masy ciała [BMI, body mass index]), biologicznych (hemoglobina glikowana[HbA1c]), terapeutycznych i patofizjologicznych (rezydualna funkcja komórek b). W celu wykrycia takich zaburzeń powinno się zalecać dodatkowe pomiary glikemii przed obiadem. Przedpołudniowe hiperglikemie wymagają zmiany w leczeniu chorego.INTRODUCTION. To determine whether, over daytime, one or several hyperglycemic excursions exist that can be general failures in the glycemic control of patients with type 2 diabetes. MATERIAL AND METHODS. In 200 non-insulin-using patients with type 2 diabetes, diurnal plasma glucose and insulin profiles were studied. Plasma glucose concentrations were measured after an overnight fast (at 8:00 A.M. immediately before breakfast), during the postprandial period (at 11:00 A.M. and 2:00 P.M.), and during the postabsorptive period (at 5:00 P.M., extended postlunch time). RESULTS. In the population considered as a whole, prelunch glucose concentrations (12.0 mmol/l) were found to be significantly increased (P < 0.0001) when compared with those observed at 8:00 A.M. (8.8 mmol/l), at 2:00 P.M. (10.5 mmol/l), and at 5:00 P.M. (8.6 mmol/l). Similar significant excursions (P < < 0.0001) in prelunch glucose were observed within subsets of patients selected from the following criteria: 1) body weight; 2) HbA1c; 3) categories of treatment and 4) residual &#946;-cell function. From the calculation of areas under the daytime glucose curves, the relative contributions of postprandial and fasting glucose to the total glucose increment were found to be similar. CONCLUSIONS. High plasma glucose excursions over morning periods seem to be a permanent failure in non&#8211;insulin-using patients with type 2 diabetes, whatever the clinical (BMI), biological (HbA1c), therapeutic, and pathophysiological (residual &#946;-cell function) status. Midmorning glucose testing should be recommended for detecting such abnormalities and for correcting them with appropriate therapies

The microRNA Signature in Response to Insulin Reveals Its Implication in the Transcriptional Action of Insulin in Human Skeletal Muscle and the Role of a Sterol Regulatory Element–Binding Protein-1c/Myocyte Enhancer Factor 2C Pathway

International audienceOBJECTIVE: Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS: We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS: Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element-binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS: This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P &lt; .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P &lt; .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P &lt; .01) or delta VF (r = 0.51; P &lt; .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF