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

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.

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Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

Case Reports in Endocrinology ◽

10.1155/2015/676191 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

David S. H. Bell

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Case Reports ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Endogenous Insulin ◽

Large Randomized Clinical Trial ◽

Endogenous Insulin Production

SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in better glycemic control in most patients but also in some patients’ less hypoglycemia, weight loss, and decreased doses of insulin. In type 1 diabetesCandida albicansvaginitis and balanitis may occur more frequently than in type 2 diabetes. These cases show that a large randomized clinical trial of SGLT2 inhibitors in type 1 diabetes needs to be performed.

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

Acta Endocrinologica ◽

10.1530/eje-19-0309 ◽

2019 ◽

Vol 181 (3) ◽

pp. 221-231 ◽

Cited By ~ 4

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.

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