C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes

Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.

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Effect of hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes: A prospective, randomised, open‐label, blinded endpoint, cross‐over study

Endocrinology Diabetes & Metabolism ◽

10.1002/edm2.258 ◽

2021 ◽

Author(s):

Radzi M. Noh ◽

Alex J. Graveling ◽

Ninian N. Lang ◽

Audrey C. White ◽

Kuan K. Lee ◽

...

Keyword(s):

Blood Flow ◽

Type 1 Diabetes ◽

Myocardial Blood Flow ◽

Myocardial Injury ◽

Open Label

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Effect of Hypoglycemia on Measures of Myocardial Blood Flow and Myocardial Injury in Adults With and Without Type 1 Diabetes: A Prospective, Randomized, Open-Label, Blinded Endpoint, Cross-Over Study

10.21203/rs.3.rs-123770/v1 ◽

2020 ◽

Author(s):

Radzi M Noh ◽

Alex J Graveling ◽

Ninian N Lang ◽

AC White ◽

Kuan Ken Lee ◽

...

Keyword(s):

Blood Flow ◽

Type 1 Diabetes ◽

Myocardial Blood Flow ◽

Coronary Flow ◽

Myocardial Injury ◽

Cardiovascular Effects ◽

Open Label ◽

Flow Reserve ◽

Diabetes Status

Abstract Aims: Hypoglycemia provokes a profound autonomic response in humans including cardiovascular effects. This study examined the effect of experimentally-induced hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.Methods and Results: In a prospective, randomized, open-label, blinded, endpoint cross-over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non-diabetic volunteers, underwent hyperinsulinemic euglycemic (blood glucose 4.5-5.5 mmol/L) and hypoglycemic (2.2-2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high-sensitivity cardiac troponin I (hs-cTnI) concentration. During euglycemia, a non-significant trend for lower CFR was observed in participants with type 1 diabetes than in those without type 1 diabetes (3.66±0.47 versus 3.92±0.85), and a non-significant lower trend also occurred during hypoglycemia (type 1 diabetes: 3.54±0.58 versus non-diabetes: 3.80±0.84). A generalized linear mixed-model analysis was performed, with diabetes status and euglycemia or hypoglycemia as factors affecting CFR. No significant statistical difference in CFR was observed for diabetes status (p=0.23) or between euglycemia and hypoglycemia (p=0.31). No changes in hs-cTnI occurred during hypoglycemia or in the recovery period (p=0.86).Conclusions: While the observed reduction in coronary flow reserve did not achieve significance during exposure to insulin-induced hypoglycemia in healthy young men with type 1 diabetes, with no evidence of myocardial injury, adverse cardiovascular effects of hypoglycemia cannot be excluded in older people who have coronary disease. Further studies are required to investigate this putative problem.

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Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus

Diabetic Medicine ◽

10.1046/j.1464-5491.2000.00274.x ◽

2000 ◽

Vol 17 (3) ◽

pp. 181-189 ◽

Cited By ~ 176

Author(s):

B. -L. Johansson ◽

K. Borg ◽

E. Fernqvist-Forbes ◽

A. Kernell ◽

T. Odergren ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

C Peptide ◽

Beneficial Effects ◽

Incipient Nephropathy

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The Effects of Plasma Insulin and Glucose on Myocardial Blood Flow in Patients With Type 1 Diabetes Mellitus

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2005.03.056 ◽

2005 ◽

Vol 46 (1) ◽

pp. 42-48 ◽

Cited By ~ 43

Author(s):

Muthayyah Srinivasan ◽

Pilar Herrero ◽

Janet B. McGill ◽

Jasper Bennik ◽

Bastiaan Heere ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Flow ◽

Type 1 Diabetes ◽

Myocardial Blood Flow ◽

Type 1 Diabetes Mellitus ◽

Plasma Insulin

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Effect of hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes: a prospective, randomized, open-label, blinded endpoint, cross-over study

10.21203/rs.3.rs-31359/v2 ◽

2020 ◽

Author(s):

Radzi M Noh ◽

AJ Graveling ◽

Ninian N Lang ◽

Audrey C White ◽

Kuan Ken Lee ◽

...

Keyword(s):

Blood Flow ◽

Type 1 Diabetes ◽

Myocardial Blood Flow ◽

Coronary Flow ◽

Myocardial Injury ◽

Cardiovascular Effects ◽

Open Label ◽

Flow Reserve ◽

Diabetes Status

Abstract Aims: Hypoglycemia provokes a profound autonomic response in humans including cardiovascular effects. This study examined the effect of experimentally-induced hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.Methods and Results: In a prospective, randomized, open-label, blinded, endpoint cross-over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non-diabetic volunteers, underwent hyperinsulinemic euglycemic (blood glucose 4.5-5.5 mmol/L) and hypoglycemic (2.2-2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high-sensitivity cardiac troponin I (hs-cTnI) concentration.During euglycemia, a non-significant trend for lower CFR was observed in participants with type 1 diabetes than in those without type 1 diabetes (3.66±0.47 versus 3.92±0.85), and a non-significant lower trend also occurred during hypoglycemia (type 1 diabetes: 3.54±0.58 versus non-diabetes: 3.80±0.84). A generalized linear mixed-model analysis was performed, with diabetes status and euglycemia or hypoglycemia as factors affecting CFR. No significant statistical difference in CFR was observed for diabetes status (p=0.23) or between euglycemia and hypoglycemia (p=0.31). No changes in hs-cTnI occurred during hypoglycemia or in the recovery period (p=0.86).Conclusions: While the observed reduction in coronary flow reserve did not achieve significance during exposure to insulin-induced hypoglycemia in healthy young men with type 1 diabetes, with no evidence of myocardial injury, adverse cardiovascular effects of hypoglycemia cannot be excluded in older people who have coronary disease. Further studies are required to investigate this putative problem.

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