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1.
Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
Afghahi, H, Nasic, S, Peters, B, Rydell, H, Hadimeri, H, Svensson, J
PloS one. 2022;(1):e0262880
Abstract
BACKGROUND The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD. METHODS 325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses. RESULTS During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death. CONCLUSION The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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2.
Alternative pre-analytic sample handling techniques for glucose measurement in the absence of fluoride tubes in low resource settings.
Nakanga, WP, Balungi, P, Niwaha, AJ, Shields, BM, Hughes, P, Andrews, RC, Mc Donald, TJ, Nyirenda, MJ, Hattersley, AT
PloS one. 2022;(2):e0264432
Abstract
INTRODUCTION Sodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda. METHODS Random (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis. RESULTS Rapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours. CONCLUSION In low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity.
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3.
Association of Serum Alkaline Phosphatase with the TG/HDL Ratio and TyG Index in Korean Adults.
Son, DH, Ha, HS, Lee, YJ
Biomolecules. 2021;(6)
Abstract
Alkaline phosphatase (ALP) has long been considered a marker of hepatobiliary and bone disorders, but recent studies have shown that increased ALP activity is correlated with various cardio-metabolic diseases. Thus, we investigated the association of serum ALP level with surrogate markers of insulin resistance such as triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C ratio) and triglyceride and glucose (TyG) index in the general population. The study included 12,868 men and women aged 19 years and older. Participants were categorized into four groups based on serum ALP level (U/L) as follows: Q1: 55-190 U/L, Q2: 191-224 U/L, Q3: 225-265 U/L, and Q4: 266-923 U/L for men, Q1: 48-161 U/L, Q2: 162-198 U/L, Q3: 199-245 U/L, Q4: 246-790 U/L for women. The insulin resistance cut-off levels were defined corresponding to the 75th percentile of the TyG index and TG/HDL-C ratio in the current samples. Odds ratios (ORs) with 95% confidence intervals (CIs) of insulin resistance according to quartile of serum ALP level were calculated using weighted multivariate logistic regression analysis. Compared with Q1, the adjusted OR (95% CI) for insulin resistance of the Q4 serum ALP group was 1.517 (1.234-1.866) in men and 1.881 (1.399-2.528) in women using the TG/HDL-C ratio and 1.374 (1.093-1.728) in men and 2.047 (1.468-2.855) in women using the TyG index after adjusting for confounding variables. Serum ALP levels are independently and positively associated with surrogate markers of insulin resistance in Korean adults.
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4.
In children and young people with type 1 diabetes using Pump therapy, an additional 40% of the insulin dose for a high-fat, high-protein breakfast improves postprandial glycaemic excursions: A cross-over trial.
Smith, TA, Smart, CE, Fuery, MEJ, Howley, PP, Knight, BA, Harris, M, King, BR
Diabetic medicine : a journal of the British Diabetic Association. 2021;(7):e14511
Abstract
AIM: To determine the insulin requirement for a high-fat, high-protein breakfast to optimise postprandial glycaemic excursions in children and young people with type 1 diabetes using insulin pumps. METHODS In all, 27 participants aged 10-23 years, BMI <95th percentile (2-18 years) or BMI <30 kg/m2 (19-25 years) and HbA1c ≤64 mmol/mol (≤8.0%) consumed a high-fat, high-protein breakfast (carbohydrate: 30 g, fat: 40 g and protein: 50 g) for 4 days. In this cross-over trial, insulin was administered, based on the insulin-to-carbohydrate ratio (ICR) of 100% (control), 120%, 140% and 160%, in an order defined by a randomisation sequence and delivered in a combination bolus, 60% ¼ hr pre-meal and 40% over 3 hr. Postprandial sensor glucose was assessed for 6 hr. RESULTS Comparing 100% ICR, 140% ICR and 160% ICR resulted in significantly lower 6-hr areas under the glucose curves: mean (95%CI) (822 mmol/L.min [605,1039] and 567 [350,784] vs 1249 [1042,1457], p ≤ 0.001) and peak glucose excursions (4.0 mmol/L [3.0,4.9] and 2.7 [1.7,3.6] vs 6.0 [5.0,6.9],p < 0.001). Rates of hypoglycaemia for 100%-160% ICR were 7.7%, 7.7%, 12% and 19% respectively (p ≥ 0.139). With increasing insulin dose, a step-wise reduction in mean glucose excursion was observed from 1 to 6 hr (p = 0.008). CONCLUSIONS Incrementally increasing the insulin dose for a high-fat, high-protein breakfast resulted in a predictable, dose-dependent reduction in postprandial glycaemia: 140% ICR improved postprandial glycaemic excursions without a statistically significant increase in hypoglycaemia. These findings support a safe, practical method for insulin adjustment for high-fat, high-protein meals that can be readily implemented in practice to improve postprandial glycaemia.
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5.
Atherogenic index of plasma is associated with major adverse cardiovascular events in patients with type 2 diabetes mellitus.
Fu, L, Zhou, Y, Sun, J, Zhu, Z, Xing, Z, Zhou, S, Wang, Y, Tai, S
Cardiovascular diabetology. 2021;(1):201
Abstract
BACKGROUND Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). METHODS This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. RESULTS AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. CONCLUSIONS This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. TRIAL REGISTRATION URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.
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6.
Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT).
Thom, G, Messow, CM, Leslie, WS, Barnes, AC, Brosnahan, N, McCombie, L, Al-Mrabeh, A, Zhyzhneuskaya, S, Welsh, P, Sattar, N, et al
Diabetic medicine : a journal of the British Diabetic Association. 2021;(8):e14395
Abstract
AIM: To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial). METHODS Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m2 , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA1c <48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2 ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss. RESULTS Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission. CONCLUSIONS Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.
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7.
Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers.
Miao, J, Bachmann, KN, Huang, S, Su, YR, Dusek, J, Newton-Cheh, C, Arora, P, Wang, TJ
Journal of the American Heart Association. 2021;(10):e017727
Abstract
Background Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids. Methods and Results This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs-CRP (high-sensitivity C-reactive protein), N-terminal pro-B-type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25-hydroxyvitamin-D [25-OH-D] ≤25 ng/mL) receiving low-dose (400 IU/d) versus high-dose (4000 IU/d) vitamin D3 for 6 months. A meta-analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25-OH-D increased in the high-dose relative to the low-dose vitamin D group (+15.5 versus +4.6 ng/mL, P<0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high-dose compared with the low-dose group (+11.3 versus -6.2 mg/dL, P<0.001). The meta-analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs-CRP, but no changes in low-density lipoprotein, after vitamin D supplementation compared with control groups. Conclusions In the DAYLIGHT randomized controlled trial, high-dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01240512.
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Risk Factors for Intraoperative Hypoglycemia in Children: A Multicenter Retrospective Cohort Study.
Riegger, LQ, Leis, AM, Golmirzaie, KH, Malviya, S
Anesthesia and analgesia. 2021;(4):1075-1083
Abstract
BACKGROUND Intraoperative hypoglycemia can result in devastating neurologic injury if not promptly diagnosed and treated. Few studies have defined risk factors for intraoperative hypoglycemia. The authors sought to characterize children with intraoperative hypoglycemia and determine independent risk factors in a multicenter cohort. METHODS This retrospective multicenter study included all patients <18 years undergoing an anesthetic from January 1, 2012, to December 31, 2016, at 12 institutions participating in the Multicenter Perioperative Outcomes Group (MPOG). The primary outcome was blood glucose <60 mg/dL (3.3 mmol/L). Data collected included patient characteristics, comorbidities, and intraoperative factors. A multivariable logistic regression model was used to identify independent predictors of intraoperative hypoglycemia. RESULTS Blood glucose was measured in 26,142 of 394,231 (6.6%) cases. Of these, 1017 (3.9%) had a glucose <60 mg/dL (3.3 mmol/L). Independent predictors for intraoperative hypoglycemia identified were age <30 days (estimated adjusted odds ratio [AOR] vs ≥5 years 4.2; 95% confidence interval [CI], 3.4-5.3), age 30 days to <5 years (estimated AOR vs ≥5 years 2.7; 95% CI, 2.3-3.2), weight for age <5th percentile (estimated AOR, 1.6; 95% CI, 1.4-1.9), American Society of Anesthesiologists (ASA) status ≥III (estimated AOR, 1.3; 95% CI, 1.1-1.6), presence of a gastric or jejunal tube (estimated AOR, 1.3; 95% CI, 1.1-1.6), poor feeding (estimated AOR, 1.5; 95% CI, 1.2-1.7), and abdominal surgery (estimated AOR, 1.4; 95% CI, 1.1-1.7). Eighty percent of hypoglycemia occurred in children <5 years of age and in children <20 kg. CONCLUSIONS Young age, weight for age <5th percentile, ASA status ≥III, having a gastric or jejunal tube, poor feeding, and abdominal surgery were risk factors for intraoperative hypoglycemia in children. Monitoring of blood glucose is recommended in these subsets of children.
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9.
Impact of endogenous insulin secretion on the improvement of glucose variability in Japanese patients with type 2 diabetes treated with canagliflozin plus teneligliptin.
Miya, A, Nakamura, A, Cho, KY, Kawata, S, Nomoto, H, Nagai, S, Sugawara, H, Taneda, S, Tsuchida, K, Omori, K, et al
Journal of diabetes investigation. 2021;(8):1395-1399
Abstract
AIMS/INTRODUCTION To identify the effect of combination therapy with a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase-4 inhibitor to a sodium-glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. MATERIALS AND METHODS A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel-group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C-peptide (CPR) divided at baseline by the median. RESULTS ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (-29.2 ± 28.3 vs -20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group (P < 0.01). CONCLUSIONS COMB would be a better protocol rather than switching teneligliptin to canagliflozin to improve daily glucose variability in patients with impaired endogenous insulin secretion.
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10.
Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double-blind placebo-controlled, randomised trial.
Snaith, JR, Samocha-Bonet, D, Evans, J, Liu, Z, Kowalski, G, Bruce, C, Holmes-Walker, DJ, Greenfield, JR
Diabetic medicine : a journal of the British Diabetic Association. 2021;(9):e14564
Abstract
BACKGROUND Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes. METHODS We will study 40 adults aged 20-55 years with Type 1 diabetes (HbA1c ≤ 80 mmol/mol [9.5%], fasting C-peptide <0.3 nmol/L) and 20 age-, gender- and body mass index (BMI)-matched controls. Insulin sensitivity will be determined by the two-step hyperinsulinaemic-euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended-release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low-dose stage of the clamp. CONCLUSION The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. TRIAL REGISTRATION ACTRN12619001440112.