C-peptide profiles in patients with non-insulin-dependent diabetes mellitus before and during insulin treatment Torbj\l=o"\rnLindstr\l=o"\m,
Hans
J Arnqvist, Johnny Ludvigsson and Henning H
von
Schenck
Departments of Internal Medicine', Pediatrics2 and Clinical Chemistry1. University Hospital, S-5S1 85 Linköping, Sweden
Lindström T, Arnqvist HJ, Ludvigsson J, von Schenck HH. C-peptide profiles in patients with noninsulin-dependent diabetes mellitus before and during insulin treatment. Acta Endocrinol 1992; 126:477-83. ISSN 0001-5598 The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C-peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C\x=req-\ peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose.
Torbjörn Lindström, Department of Internal Medicine, University Hospital,
In patients with non-insulin-dependent diabetes mellitus (NIDDM) there is often a slow deterioration of endoge¬ nous insulin secretion (1), and when secondary failure to oral hypoglycémie agents develops insulin treatment must be considered (2-5). Insulin treatment can affect the endogenous insulin secretion in several ways. On lowering blood glucose concentration the glucose stimu¬ lus to insulin secretion is reduced (6). Insulin treatment of NIDDM patients has been reported as reducing the glucose toxicity in the beta-cell (7-8) and improving endogenous insulin secretion (9-12). Insulin treatment can reduce insulin resistance of peripheral tissues, thereby enhancing insulin action and decreasing the amount of insulin needed for
glucose values (9, 10).
maintaining normal blood
Whether
or not exogenous insulin has a direct effect on endogenous insulin secre¬ tion is controversial (13-17). Diurnal C-peptide profiles have been studied in healthy control subjects and in NIDDM patients treated with diet or diet combined with oral hypoglycémie agents (10, 18-20), but little is known about endoge¬ nous insulin secretion during insulin treatment of NIDDM patients. Holman et al. (20) reported that Cpeptide concentrations in patients treated twice daily with long-acting insulin (Ultralente) and regular insulin were lower than in patients receiving combined treat¬ ment with sulphonylureas. Blackshear and co-workers
S-581 85
Linköping,
Sweden
(21, 22) compared C-peptide profiles of NIDDM patients treated by a single injection of lente and ultralente insulin with those in patients equipped with an intra¬ venous insulin pump. There is also a report of a 5-h profile following a mixed meal (23), showing a smaller Cpeptide response on insulin treatment than on treatment with diet or diet and sulphonylurea. The aim of the present investigation was to study how insulin treatment of patients with NIDDM and secondary failure to oral hypoglycémie agents affects endogenous insulin secretion, and whether intensive and conven¬ tional insulin regimens differ in this respect. We also evaluated the glucagon C-peptide test for determination of endogenous insulin secretion in relation to the 24-h C-peptide profile before and during insulin treatment. Patients and methods Patients The series
10 patients (4M and 6F; age mean±SEM; body mass index kg/m2, range 20.3-28.8). Their known diabetes duration was 9.0±0.5 (range 7-12) years and
57.6±2.5 24.3±0.8
comprised years,
the duration of treatment with oral hypoglycémie agents 6.1 ±0.9 years. AH had previously responded to treat¬ ment with diet and oral hypoglycémie agents. Nine
478
Torbjörn Lindström et al.
ACTA ENDOCRINOLOGICA 1992, 126
patients were treated with glibenelamid (7-14 mg daily) and one with glipizid (17.5 mg daily); three of them also
daily). All nephropathy (no albuminuria, normal received metformin (1.0 g
were
without
serum
creati-
nine). The HbAic in patients treated with oral agents was 8.8 ±0.2%; this was reduced to 5.7±0.1 on 2-dose (p
Hans
J Arnqvist, Johnny Ludvigsson and Henning H
von
Schenck
Departments of Internal Medicine', Pediatrics2 and Clinical Chemistry1. University Hospital, S-5S1 85 Linköping, Sweden
Lindström T, Arnqvist HJ, Ludvigsson J, von Schenck HH. C-peptide profiles in patients with noninsulin-dependent diabetes mellitus before and during insulin treatment. Acta Endocrinol 1992; 126:477-83. ISSN 0001-5598 The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C-peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C\x=req-\ peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose.
Torbjörn Lindström, Department of Internal Medicine, University Hospital,
In patients with non-insulin-dependent diabetes mellitus (NIDDM) there is often a slow deterioration of endoge¬ nous insulin secretion (1), and when secondary failure to oral hypoglycémie agents develops insulin treatment must be considered (2-5). Insulin treatment can affect the endogenous insulin secretion in several ways. On lowering blood glucose concentration the glucose stimu¬ lus to insulin secretion is reduced (6). Insulin treatment of NIDDM patients has been reported as reducing the glucose toxicity in the beta-cell (7-8) and improving endogenous insulin secretion (9-12). Insulin treatment can reduce insulin resistance of peripheral tissues, thereby enhancing insulin action and decreasing the amount of insulin needed for
glucose values (9, 10).
maintaining normal blood
Whether
or not exogenous insulin has a direct effect on endogenous insulin secre¬ tion is controversial (13-17). Diurnal C-peptide profiles have been studied in healthy control subjects and in NIDDM patients treated with diet or diet combined with oral hypoglycémie agents (10, 18-20), but little is known about endoge¬ nous insulin secretion during insulin treatment of NIDDM patients. Holman et al. (20) reported that Cpeptide concentrations in patients treated twice daily with long-acting insulin (Ultralente) and regular insulin were lower than in patients receiving combined treat¬ ment with sulphonylureas. Blackshear and co-workers
S-581 85
Linköping,
Sweden
(21, 22) compared C-peptide profiles of NIDDM patients treated by a single injection of lente and ultralente insulin with those in patients equipped with an intra¬ venous insulin pump. There is also a report of a 5-h profile following a mixed meal (23), showing a smaller Cpeptide response on insulin treatment than on treatment with diet or diet and sulphonylurea. The aim of the present investigation was to study how insulin treatment of patients with NIDDM and secondary failure to oral hypoglycémie agents affects endogenous insulin secretion, and whether intensive and conven¬ tional insulin regimens differ in this respect. We also evaluated the glucagon C-peptide test for determination of endogenous insulin secretion in relation to the 24-h C-peptide profile before and during insulin treatment. Patients and methods Patients The series
10 patients (4M and 6F; age mean±SEM; body mass index kg/m2, range 20.3-28.8). Their known diabetes duration was 9.0±0.5 (range 7-12) years and
57.6±2.5 24.3±0.8
comprised years,
the duration of treatment with oral hypoglycémie agents 6.1 ±0.9 years. AH had previously responded to treat¬ ment with diet and oral hypoglycémie agents. Nine
478
Torbjörn Lindström et al.
ACTA ENDOCRINOLOGICA 1992, 126
patients were treated with glibenelamid (7-14 mg daily) and one with glipizid (17.5 mg daily); three of them also
daily). All nephropathy (no albuminuria, normal received metformin (1.0 g
were
without
serum
creati-
nine). The HbAic in patients treated with oral agents was 8.8 ±0.2%; this was reduced to 5.7±0.1 on 2-dose (p
