Post-exercise glycemic control in type 1 diabetes is associated with residual ꞵ-cell function

Objective To investigate the impact of residual ꞵ-cell function on continuous glucose monitor (CGM) outcomes following acute exercise in people with Type 1 diabetes. Research Design and Methods Thirty participants with type 1 diabetes for ≥3 years were recruited. Firstly, participants wore a blinded CGM for 7 days of free-living data capture. Secondly, a 3 hour mixed meal test, assessed stimulated C-peptide and glucagon. Peak C-peptide was used to allocate participants into undetectable (Cpepund <3 pmol/L), low (Cpeplow 3–200 pmol/L) or high C-peptide groups (Cpephigh >200 pmol/L). Finally, participants completed 45 minutes of incline treadmill walking at 60%VO2peak followed by a further 48 hours’ CGM capture. Results CGM parameters were comparable across groups during the free-living observation week. In the 12 (12hr) and 24 hours (24hr) post-exercise periods the Cpephigh group had significantly greater amount of time spent with glucose 3.9-10 mmol/L (12hr: 73.5±27.6%, 24hr: 76.3±19.2%) compared to Cpeplow (12hr: 43.6±26.1%, p=0.027, 24hr: 52.3±25.0%, p=0.067) or Cpepund (40.6±17.0%, p=0.010, 24hr: 51.3±22.3%, p=0.041). Time spent in hyperglycemia (12hr and 24hr glucose >10 and >13.9 mmol/L, p<0.05) and glycemic variability (12hr and 24hr SD, p<0.01) were significantly lower in the Cpephigh group compared to Cpepund and Cpeplow. Change in CGM outcomes from pre to 24hr post-exercise was divergent: Cpepund and Cpeplow experienced worsening (glucose 3.9-10 mmol/L: -9.1% and -16.2% respectively), with Cpephigh experiencing improvement (+12.1%)(p=0.017). Conclusions Residual ꞵ-cell function may partially explain the inter-individual variation in the acute glycemic benefits of exercise in individuals with type 1 diabetes. Quantifying C-peptide could aid in providing personalized and targeted support for exercising patients.

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Post-exercise glycemic control in type 1 diabetes is associated with residual ꞵ-cell function

10.2337/figshare.12616118 ◽

2020 ◽

Author(s):

Guy S Taylor ◽

Kieran Smith ◽

Tess E Capper ◽

Jadine H Scragg ◽

Ayat Bashir ◽

...

Keyword(s):

Type 1 Diabetes ◽

Acute Exercise ◽

Cell Function ◽

Glycemic Variability ◽

Free Living ◽

Continuous Glucose Monitor ◽

Post Exercise ◽

C Peptide ◽

The Impact

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Measurement Of Peak C-Peptide At Diagnosis Informs Glycemic Control But Not Hypoglycemia In Adults With Type 1 Diabetes

Journal of the Endocrine Society ◽

10.1210/jendso/bvab127 ◽

2021 ◽

Author(s):

Alice L J Carr ◽

Richard A Oram ◽

Shannon M Marren ◽

Timothy J McDonald ◽

Parth Narendran ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Dose ◽

Glucose Monitoring ◽

Glycemic Variability ◽

Newly Diagnosed ◽

C Peptide ◽

Glucose Levels ◽

Normal Glucose ◽

The Impact

Abstract Context High residual C-peptide in longer duration type 1 diabetes associates with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close-to-diagnosis. Objective Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with type 1 diabetes, we aimed to explore if variation in C-peptide close-to-diagnosis influenced glycemic variability and risk of hypoglycemia. Design We studied newly diagnosed adults with type 1 diabetes who wore a Dexcom G4 CGM for 7 days as part the EXTOD study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants. Results For every 100 pmol/l increase in peak C-peptide, percentage time spent range 3.9-10 mmol/l was increased by 2.4% [95% CI: 0.5,4.3], p=0.01) with a reduction in time spent in level 1 hyperglycemia (> 10 mmol/l) and level 2 hyperglycemia (> 13.9 mmol/l) by 2.6% [95% CI: -4.9, -0.4, p=0.02) and 1.3% [95% CI: -2.7, -0.006], p= 0.04) respectively. Glucose levels were on average lower by 0.19 mmol/l ([95 % CI: -0.4,0.02], p=0.06) and standard deviation reduced by 0.14 [95% CI: -0.3, -0.02], p=0.02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (p=0.97) or hypoglycemic risk (p=0.72). There was no association between peak C-peptide and insulin dose adjusted HbA1c (IDAA1c, p=0.45). Conclusions C-peptide associates with time spent in normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with type 1 diabetes.

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Ketogenic Diet in a Patient With Type 1 Diabetes Mellitus With Hypoglycemia Unawareness

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.939 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A460-A460

Author(s):

Mohamad Anas Sukkari ◽

Lucia Cotten ◽

Murtaza Alam ◽

Emily Temponi ◽

Priya D John ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycemic Control ◽

Ketogenic Diet ◽

Severe Hypoglycemia ◽

Glycemic Variability ◽

Glucose Variability ◽

Continuous Glucose Monitor ◽

Hypoglycemia Unawareness ◽

The Impact

Abstract Introduction: The high fat, low carbohydrate ketogenic diet has become increasingly popular in recent years for weight loss and glycemic control in patients with type 2 diabetes. Although prior studies have suggested this diet can improve glycemic control and decrease glucose variability, the impact of a ketogenic diet on rates of hypoglycemia in patients with hypoglycemia unawareness is not well described. Case Description: Our patient is a 37 year-old woman with Type 1 diabetes for 13 years complicated by hypoglycemia unawareness with HbA1c of 7.7%. Her insulin treatment regimen included insulin glargine 22 units daily, insulin aspart using a 1:15 carbohydrate ratio for prandial insulin dosing with a correction factor of 90. She had 5 episodes of severe hypoglycemia within the previous 3 months. The patient decided to resume a ketogenic diet given her previous improvement in glycemic control. Ketosis was confirmed using urine ketone strips performed by the patient. After 2 weeks on the ketogenic diet, a professional blinded continuous glucose monitor (CGM) was used for 4 weeks to monitor glycemic control. CGM data for weeks 1 and 2 showed overall stability of time in target glucose range [TIR, 60% and 69%, respectively], with a slight increase in time spent below range [TBR, 13% and 17%, respectively]. During week 3, the patient experienced a significant decline in TIR to 31%, and associated increase in hypoglycemia (TBR, 13% to 28%). In addition, glycemic variability increased during this time [CV (coefficient of variation), 40.6% during week 1 to 58.1% during week 3]. Patient did not experience symptoms concerning for DKA, and continued to have asymptomatic hypoglycemia despite reductions in her insulin doses during week 3. Following these dose adjustments, CGM data during week 4 were similar to week 1 (TIR 65%, TBR 10%, CV 35%). Patient stopped following the ketogenic diet after 6 weeks due to social factors. Conclusion: A ketogenic diet was associated with increased frequency of hypoglycemic events. In a patient with Type 1 diabetes and hypoglycemia unawareness, use of ketogenic diet may further increase the risk of severe hypoglycemia.

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1917-P: Alpha-Cell Function in Patients with Type 1 Diabetes Is Compromised with Different Levels of Residual C-Peptide

Diabetes ◽

10.2337/db20-1917-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1917-P

Author(s):

LINGYU ZHANG ◽

YUWEN SHI ◽

YITING HUANG ◽

QIZHEN HU ◽

YAO QIN ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cell Function ◽

Alpha Cell ◽

C Peptide ◽

Alpha Cell Function ◽

Different Levels

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Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes

Nutrients ◽

10.3390/nu13114154 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4154

Author(s):

Emily Bell ◽

Sabrina Binkowski ◽

Elaine Sanderson ◽

Barbara Keating ◽

Grant Smith ◽

...

Keyword(s):

Type 1 Diabetes ◽

Individual Variability ◽

Living Conditions ◽

Optimal Time ◽

Daily Routine ◽

Free Living ◽

Continuous Glucose Monitor ◽

Time To Peak ◽

Free Living Conditions

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8–15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs within-person SD; controlled breakfast 18.5 vs 38.9 minutes; FLB 14.1 vs 49.6 minutes; FLD 5.7 vs 64.5 minutes). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.

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Association of glycemic variability and hypoglycemia with distal symmetrical polyneuropathy in adults with type 1 diabetes

Scientific Reports ◽

10.1038/s41598-021-02258-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ziyang Shen ◽

Hemin Jiang ◽

Rong Huang ◽

Yunting Zhou ◽

Qian Li ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycemic Variability ◽

Mean Amplitude ◽

Cross Sectional Study ◽

Cross Sectional ◽

C Peptide ◽

Nocturnal Hypoglycemia ◽

Increased Risk ◽

Distal Symmetrical Polyneuropathy

AbstractPrevious studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.

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Alterations in Skeletal Muscle Repair in Young Adults with Type 1 Diabetes Mellitus

AJP Cell Physiology ◽

10.1152/ajpcell.00322.2021 ◽

2021 ◽

Author(s):

Athan G. Dial ◽

Grace K. Grafham ◽

Cynthia MF. Monaco ◽

Jennifer Voth ◽

Linda Brandt ◽

...

Keyword(s):

Electron Microscopy ◽

Skeletal Muscle ◽

Type 1 Diabetes ◽

Young Adults ◽

Gene Networks ◽

Vastus Lateralis ◽

Post Exercise ◽

Ultrastructural Damage ◽

The Impact

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here we investigated the impact of damaging exercise (eccentric quadriceps contractions) in eighteen physically-active young adults with and without T1D. Pre- and post-exercise (48h and 96h), participants provided blood samples, vastus lateralis biopsies and performed maximal voluntary quadriceps contractions (MVC). Skeletal muscle sarcolemmal integrity, extracellular matrix content (ECM), and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Post-exercise, MVC was decreased in both groups, but T1D subjects exhibited moderately lower strength recovery at both 48h and 96h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in T1D participants at rest, and exhibited a small elevation 96h post-exercise. T1D participants showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar T1D cohorts. Our findings indicate that skeletal muscle in young adults with moderately-controlled T1D is altered after damaging exercise; suggesting that longer recovery times following intense exercise may be necessary.

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Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

BMC Pediatrics ◽

10.1186/s12887-020-02339-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Anne Julie Overgaard ◽

Jens Otto Broby Madsen ◽

Flemming Pociot ◽

Jesper Johannesen ◽

Joachim Størling

Keyword(s):

Type 1 Diabetes ◽

Cell Function ◽

Disease Onset ◽

Newly Diagnosed ◽

Β Cell ◽

Entire Study ◽

C Peptide ◽

Disease Remission ◽

Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

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Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

International Journal of Molecular Sciences ◽

10.3390/ijms21249723 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9723

Author(s):

Aleksandra Ryk ◽

Aleksandra Łosiewicz ◽

Arkadiusz Michalak ◽

Wojciech Fendler

Keyword(s):

Type 1 Diabetes ◽

Growth Factor ◽

Transforming Growth Factor ◽

Negative Impact ◽

Current Knowledge ◽

Microvascular Complications ◽

C Peptide ◽

Increased Risk ◽

The Impact

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

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