scholarly journals Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Mikkel B Christensen ◽  
Asger B Lund ◽  
Niklas R Jørgensen ◽  
Jens J Holst ◽  
Tina Vilsbøll ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Resorption ◽  
Bone Resorption Marker ◽  
Bone Biomarkers ◽  
Short Term ◽  
Collagen Crosslinks ◽  
Procollagen Type ◽  
Placebo Infusion

Abstract Context In healthy individuals, glucose-dependent insulinotropic polypeptide (GIP) enhances insulin secretion and reduces bone resorption by up to 25% estimated by absolute placebo-corrected changes in carboxy-terminal type 1 collagen crosslinks (CTX) during GIP and glucose administration. In patients with type 2 diabetes (T2D), GIP’s insulinotropic effect is impaired and effects on bone may be reduced. Objective To investigate GIP’s effect on bone biomarkers in patients with T2D. Design Randomized, double-blinded, crossover study investigating 6 interventions. Patients Twelve male patients with T2D. Interventions A primed continuous 90-minute GIP infusion (2 pmol/kg/min) or matching placebo (saline) administered at 3 plasma glucose (PG) levels (i.e., paired days with “insulin-induced hypoglycemia” (PG lowered to 3 mmol/L), “fasting hyperglycemia” (mean PG ~8 mmol/L), or “aggravated hyperglycemia” (mean PG ~12 mmol/L). Main Outcome Measures Bone biomarkers: CTX, procollagen type 1 N-terminal propeptide (P1NP) and PTH. Results On days with insulin-induced hypoglycemia, CTX was suppressed by up to 40 ± 15% during GIP administration compared with 12 ± 11% during placebo infusion (P < 0.0001). On days with fasting hyperglycemia, CTX was suppressed by up to 36 ± 15% during GIP administration, compared with 0 ± 9% during placebo infusion (P < 0.0001). On days with aggravated hyperglycemia, CTX was suppressed by up to 47 ± 23% during GIP administration compared with 10 ± 9% during placebo infusion (P = 0.0005). At all glycemic levels, P1NP and PTH concentrations were similar between paired days after 90 minutes. Conclusions Short-term GIP infusions reduce bone resorption by more than one-third (estimated by absolute placebo-corrected CTX reductions) in patients with T2DM, suggesting preserved bone effects of GIP in these patients. Précis Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels.

scholarly journals Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

2021 ◽  
Vol 9 (1) ◽  
pp. e002035
Author(s):  
Merel M Ruissen ◽  
Hannah Regeer ◽  
Cyril P Landstra ◽  
Marielle Schroijen ◽  
Ingrid Jazet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Weight Gain ◽  
Glycemic Control ◽  
Perceived Stress ◽  
Medical Center ◽  
Short Term ◽  
Design And Methods

IntroductionLockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methodsWe performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.ResultsIn total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: −0.39% (−4.3 mmol/mol) (p<0.0001 and type 2 diabetes: −0.62% (−6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001).ConclusionsAn increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption Independently of Insulin and Glycemia

2017 ◽  
Vol 103 (1) ◽  
pp. 288-294 ◽  
Author(s):  
Mikkel B Christensen ◽  
Asger Lund ◽  
Salvatore Calanna ◽  
Niklas R Jørgensen ◽  
Jens J Holst ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Insulin Release ◽  
Plasma Glucose ◽  
Saline Infusion ◽  
Bone Homeostasis ◽  
Collagen Crosslinks ◽  
Procollagen Type ◽  
Endogenous Insulin ◽  
Gut Hormone

Abstract Context The gut hormone glucose-dependent insulinotropic polypeptide (GIP) causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX). Objective To study if GIP affects bone homeostasis biomarkers independently of insulin release and glycemic level. Design Randomized, double-blinded, crossover study with 5 study days. Patients Ten male C-peptide-negative patients with type 1 diabetes. Interventions On 3 matched days with “low glycemia” (plasma glucose in the interval 3 to 7 mmol/L for 120 minutes), we administered intravenous (IV) GIP (4 pmol × kg−1 × min−1), glucagon-like peptide 1 (1 pmol × kg−1 × min−1), or placebo (saline), and on 2 matched days with “high glycemia” (plasma glucose 12 mmol/L for 90 minutes), we administered either GIP or saline. Main Outcome Measures CTX, procollagen type 1 N-terminal propeptide (P1NP), and parathyroid hormone (PTH). Results During low glycemia: GIP progressively suppressed CTX from baseline by up to 59 ± 18% compared with 24 ± 10% during saline infusion (P &lt; 0.0001). Absolute values of P1NP and PTH did not differ between days. During high glycemia: GIP suppressed CTX from baseline by up to 59 ± 19% compared with 7 ± 9% during saline infusion (P &lt; 0.0001). P1NP did not differ between days. GIP suppressed PTH after 60 minutes compared with saline (P &lt; 0.01), but this difference disappeared after 90 minutes. Conclusions Short-term GIP infusions robustly reduce bone resorption independently of endogenous insulin secretion and during both elevated and low plasma glucose, but have no effect on P1NP or PTH after 90 minutes.

scholarly journals The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes

2019 ◽  
Vol 181 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Katrine Hygum ◽  
Jakob Starup-Linde ◽  
Torben Harsløf ◽  
Niklas Rye Jørgensen ◽  
Bolette Hartmann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Bone Formation ◽  
Bone Turnover ◽  
Diurnal Variation ◽  
Repeated Measures ◽  
Procollagen Type ◽  
Patients With Diabetes

Objective Bone turnover has a diurnal variation influenced by food intake, incretin hormones, the sympathetic nervous system and osteocyte function. The aim of the study was to compare diurnal variation in bone turnover in patients with diabetes and controls. Design A clinical 24-h study with patients with type 1 diabetes (n = 5), patients with type 2 diabetes (n = 5) and controls (n = 5). Methods Inclusion criterion: age >50 years. Exclusion criteria: diseases/medication that affect bone metabolism or recent use of incretin-based drugs. We drew blood samples hourly during the day and every 3 h during the night. We served an identical diet on all study days. We used repeated-measures one-way ANOVA to compare the levels of the investigated markers, and we quantified the effect of time by comparing group mean standard deviations. Results The bone formation marker procollagen type 1 N-terminal propeptide showed a significant interaction between time and group (P = 0.01), and the mean standard deviation was lower in patients with type 2 diabetes compared with controls (P = 0.04) and patients with type 1 diabetes (P = 0.02). Other markers of bone formation and resorption showed significant effect of time. Levels of glucagon-like peptide-2, glucose-dependent insulinotropic peptide and sclerostin only showed significant effect of time (all P values 0.01), but levels of sclerostin tended to being highest in type 2 diabetes and lowest in controls. Conclusions The diurnal variation in bone formation is attenuated in patients with type 2 diabetes. This is not explained by changes in incretin hormone levels, but possibly mediated by sclerostin.

scholarly journals An Important Form of Diabetes for Clinicians: Ketosis-Prone Diabetes

2021 ◽  
pp. 1-4
Author(s):  
Esra Ekiz ◽  
Tahsin Celepkolu ◽  
Yavuz Karahan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Insulin Treatment ◽  
Short Term ◽  
Hybrid Form ◽  
Important Form

Ketosis-prone diabetes (KPD) is defined as a hybrid form of diabetes mellitus, which is predominantly seen in overweight-to-obese men. Although the diagnosis is based on diabetic ketoacidosis (DKA) as a presenting feature, which also is characteristic of type 1 diabetes, the course of the disease differs from type 1. Recognition of this form by the clinicians is important as these patients are negative for autoantibodies and share the characteristics of type 2 diabetes during follow-up. Here we report 2 cases of KPD presenting with DKA and maintaining normoglycemia without insulin after receiving short-term intensive insulin treatment.

scholarly journals The Efficacy of Mobile Phone Apps for Lifestyle Modification in Diabetes: Systematic Review and Meta-Analysis (Preprint)

2018 ◽  
Author(s):  
Xinghan Wu ◽  
Xitong Guo ◽  
Zhiwei Zhang
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Mobile Phone ◽  
Lifestyle Modification ◽  
Meta Analysis ◽  
Short Term

BACKGROUND Diabetes and related complications are estimated to cost US $727 billion worldwide annually. Type 1 diabetes, type 2 diabetes, and gestational diabetes are three subtypes of diabetes that share the same behavioral risk factors. Efforts in lifestyle modification, such as daily physical activity and healthy diets, can reduce the risk of prediabetes, improve the health levels of people with diabetes, and prevent complications. Lifestyle modification is commonly performed in a face-to-face interaction, which can prove costly. Mobile phone apps provide a more accessible platform for lifestyle modification in diabetes. OBJECTIVE This review aimed to summarize and synthesize the clinical evidence of the efficacy of mobile phone apps for lifestyle modification in different subtypes of diabetes. METHODS In June 2018, we conducted a literature search in 5 databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and PsycINFO). We evaluated the studies that passed screening using The Cochrane Collaboration’s risk of bias tool. We conducted a meta-analysis for each subtype on the mean difference (between intervention and control groups) at the posttreatment glycated hemoglobin (HbA1c) level. Where possible, we analyzed subgroups for short-term (3-6 months) and long-term (9-12 months) studies. Heterogeneity was assessed using the I2 statistic. RESULTS We identified total of 2669 articles through database searching. After the screening, we included 26 articles (23 studies) in the systematic review, of which 18 studies (5 type 1 diabetes, 11 type 2 diabetes, and 2 prediabetes studies) were eligible for meta-analysis. For type 1 diabetes, the overall effect on HbA1c was statistically insignificant (P=.46) with acceptable heterogeneity (I2=39%) in the short-term subgroup (4 studies) and significant heterogeneity between the short-term and long-term subgroups (I2=64%). Regarding type 2 diabetes, the overall effect on HbA1c was statistically significant (P<.01) in both subgroups, and when the 2 subgroups were combined, there was virtually no heterogeneity within and between the subgroups (I2 range 0%-2%). The effect remained statistically significant (P<.01) after adjusting for publication bias using the trim and fill method. For the prediabetes condition, the overall effect on HbA1c was statistically insignificant (P=.67) with a large heterogeneity (I2=65%) between the 2 studies. CONCLUSIONS There is strong evidence for the efficacy of mobile phone apps for lifestyle modification in type 2 diabetes. The evidence is inconclusive for the other diabetes subtypes.

SGLT2 Inhibitors Increase Bone Strength by Increasing Procollagen Type 1 Amino-Terminal Propeptide in Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1157-P
Author(s):  
MASATAKA KUSUNOKI ◽  
YUKIE NATSUME ◽  
TETSURO MIYATA ◽  
YOSHIHARU OSHIDA
Keyword(s):  
Type 2 Diabetes ◽  
Bone Strength ◽  
Sglt2 Inhibitors ◽  
Procollagen Type ◽  
Amino Terminal

scholarly journals Effect of carbohydrate feeding on the bone metabolic response to running

2015 ◽  
Vol 119 (7) ◽  
pp. 824-830 ◽  
Author(s):  
Craig Sale ◽  
Ian Varley ◽  
Thomas W. Jones ◽  
Ruth M. James ◽  
Jonathan C. Y. Tang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Metabolic Response ◽  
Maximal Oxygen Consumption ◽  
Area Under The Curve ◽  
Acute Effect ◽  
Treadmill Running ◽  
Short Term ◽  
Procollagen Type ◽  
Carbohydrate Feeding

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass−1·h−1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover – a systematic review and meta-analysis

2017 ◽  
Vol 176 (3) ◽  
pp. R137-R157 ◽  
Author(s):  
Katrine Hygum ◽  
Jakob Starup-Linde ◽  
Torben Harsløf ◽  
Peter Vestergaard ◽  
Bente L Langdahl
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Meta Analysis ◽  
Patients With Diabetes ◽  
Low Bone Turnover

Objective To investigate the differences in bone turnover between diabetic patients and controls. Design A systematic review and meta-analysis. Methods A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms ‘diabetes mellitus’ and ‘bone turnover’, ‘sclerostin’, ‘RANKL’, ‘osteoprotegerin’, ‘tartrate-resistant acid’ and ‘TRAP’ were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. Results A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (−0.10 ng/mL (−0.12, −0.08)) and the bone formation markers osteocalcin (−2.51 ng/mL (−3.01, −2.01)) and procollagen type 1 amino terminal propeptide (−10.80 ng/mL (−12.83, −8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (−0.31 U/L (−0.56, −0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Conclusions Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.

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