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PubMed1981

Effects of sulfonylurea on the secretion and disposition of insulin and C-peptide.

In an attempt to examine the influence of sulfonylurea on the secretion, disposition and effect of insulin, 9 diabetic patients were studied during three one-month medications with (a) chlorpropamide (t1/2 greater than 24 h) once daily, (b) glipizide (t1/2 2-4 h) once daily, and (c) glipizide in divided dosage. The food intake of each patient was identical during each examination period. Blood concentrations of C-peptide, insulin, glucose, and drugs were determined before and after breakfast and lunch on the 4th day of each examination period. As expected, once-daily administration of glipizide led to higher after-breakfast concentrations of the drug than when the dose was divided. However, the C-peptide changes following breakfast were similar both during these two treatments and also during chlorpropamide, indicating that the amounts of insulin released from the pancreas were equivalent. In spite of this, glipizide once daily yielded 60-70% more insulin in systemic blood following breakfast than did the two other treatments. Reasonably, this signifies that the hepatic extraction of insulin was reduced during once-daily glipizide, allowing more insulin to reach systemic circulation. In addition, this was found to promote a more effective utilization of glucose following breakfast. Following lunch, the C-peptide release, the plasma insulin increase and the blood glucose reduction were greater when glipizide was given in divided dosage than when once-daily glipizide or chlorpropamide was employed. This occurred even though the after-lunch concentration of glipizide in systemic blood was lower rather than higher during divided than during once-daily administration. This supports the notion that the effect of orally administered sulfonylurea is determined not only by its concentration in systemic blood but also by its gastroenterohepatic appearance. Glipizide may offer greater therapeutic flexibility than chlorpropamide, but further studies are required to define the optimum choice and use of sulfonylureas.

Aged↗
PubMed1989

Effects of ethanol and inhibitors of its metabolism on the circulating levels of Met-enkephalin in greyhounds.

The mechanisms involved in the release of Met-enkephalin-like immunoreactivity (MLI) into the circulation following oral administration of ethanol and chlorpropamide were investigated in dogs. The origin of plasma MLI and the sites where it may be metabolized were also studied. Moreover, the molecular nature of circulating MLI was characterized. In conscious animals oral administration of ethanol (0.15 ml/kg) led to a significant (P less than 0.01) rise in plasma MLI concentrations in chlorpropamide-pretreated animals from a basal level of 43 +/- 6 (mean +/- S.E.M.) to a peak of 66 +/- 8 ng/l. Similar rises in MLI concentrations were observed following administration of ethanol with disulfiram and ethanol with chlorpropamide and captopril. In contrast, the administration of ethanol alone or ethanol with 4-methylpyrazole resulted in a decrease in plasma MLI concentrations. Comparisons of two different doses of i.v. acetaldehyde, the first metabolite of ethanol, showed that plasma MLI concentrations rose significantly (P less than 0.05) only after the larger dose (8 mg/kg), rising from 45 +/- 7 to 81 +/- 18 ng/l. These results suggest that acetaldehyde is the active component in the chlorpropamide + ethanol-induced MLI secretion. Plasma MLI was also measured following acetaldehyde infusion in adrenalectomized dogs with and without hexamethonium treatment. Acute bilateral adrenalectomy resulted in a decrease (P less than 0.05) in plasma MLI concentrations, but the levels remained detectable. Moreover, subsequent acetaldehyde infusion led to rises in plasma MLI similar to those observed in animals with intact adrenals. These MLI responses were not altered by the concurrent i.v. administration of hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1977

Measurement of antidiabetic sulfonylureas in serum by gas chromatography with electron-capture detection.

A method is described for measurement of chlorpropamide, tolbutamide, and the tolbutamide metabolites hydroxymethyltolbutamide and carbotytolbutamide in blood. It consists of formation of the thermally stable methyl-trifluoroacetyl derivatives of chlorpropamide and tolbutamide, and the methyl-heptafluorobutyryl derivatives of hydroxymethyltolbutamide and carboxytolbutamide, which are then analyzed by electron-capture gas chromatography. Measurements of blood levels of the compounds with this method have been verified by quantitation of the same samples using gas chromatography-mass spectrometry in the mass fragmentography mode. Blood level values and beta-phase half-time disappearance rates of chlorpropamide, tolbutamide, hydroxymethyltolbutamide, and carboxytolbutamide were measured in normal volunteers following an oral dose of chlorpropamide or tolbutamide. Blood levels of the four compounds were also determined in a few diabetics receiving continuous daily treatment.

Chemical Phenomena↗
PubMed1988

[Effects of analogues and drugs on arginine vasopressin receptor binding in rat renal tubular basolateral membrane].

The methods of basolateral membrane isolation from rat kidney and 3H-AVP receptor assay using this basolateral membrane preparation were established. Then, the effects of analogues and drugs on AVP-receptor binding were studied. Specific 3H-AVP binding was inhibited by LVP, dDAVP and oxytocin in that order. Among the various agonistic or antagonistic drugs to AVP (fluoride, cyclophosphamide, mechlorethamine, chlorpropamide), only chlorpropamide inhibited 3H-AVP binding to the membrane. The Kd value calculated by Scatchard analysis was 1.30 +/- 0.28 nM (n = 4, M +/- SD), and it was increased to 2.69 +/- 0.32 nM (n = 5, M +/- SD) by adding 1 mM of chlorpropamide, while Bmax was unchanged. Our data show that 1 mM chlorpropamide decreases receptor affinity for AVP, and alters AVP-receptor binding in a competitive manner.

Animals↗
PubMed1979

Effects of long term sulfonylurea therapy on plasma insulin and fasting lipid levels.

Insulin secretion was studied before and after the control of hyperglycemia in fourteen maturity onset male non-obese diabetics. Optimum control of hyperglycemia was achieved by the addition of the sulfonylurea chlorpropamide to dietary treatment. One patient was a primary treatment failure, but nine out of thirteen had excellent control of hyperglycemia. A standardized oral glucose tolerance test (GTT) was performed before and after eight months of individualized therapy with the sulfonylurea. The GTT was repeated with each patient taking his usual dose of chlorpropamide 90 min prior to the administrationo f the glucose load. In the baseline test glucose levels rose from 135.6 +/- 9.9 mg/dl to a peak level of 268.8 +/- 17.7 mg/dl at 120 min. After control of hyperglycemia glucose levels were significantly lower at 0, 30 and 60 min, and rose from 106.8 +/- 8.5 mg/dl to a maximum of 224.5 +/- 17.3 mg/dl at 120 min. Plasma insulin response was unchanged. Fasting serum cholesterol, triglyceride and total lipid levels changed only minimally during therapy. It is concluded that lowered serum glucose levels after long term treatment with chlorpropamide occured while plasma insulin response to glucose was no greater than before treatment. These findings may be explained by an extrapancreatic effect of the drug or by an indirect result of chlorpropamide induced insulin release which occured earlier in the course of therapy.

Aged↗
PubMed1979

Effect of propranolol on drug-induced and physiological glycogenolysis in the liver.

The beta-adrenergic blocking agent propranolol had in itself no notable influence on the blood glucose level in rats, but in combination with chlorpropamide it considerably delayed and enhanced the hypoglycaemic and liver glycogenolysis depressing actions of chlorpropamide. This effect was still more pronounced when the rats were treated in addition to propranolol and chlorpropamide with thyroxine or glanduitrine, which in themselves act as stimulators of liver glycogenolysis. The simultaneous administration of propranolol and chlorpropamide depressed considerably the liver glycogenolysis induced by prolonged fasting and inhibited completely the liver glycogenolysis observed after hepatectomy. The reports available in the literature on propranolol-precipitated hypoglycaemia in patients are surveyed and it is supposed that the beta-adrenergic blocking agent produces hypoglycaemia primarily through the depression of liver glycogenolysis. This observation supports the hypothesis that the adrenergic beta-receptors play an important role in the sympathetic control of liver glycogenolysis.

Animals↗
PubMed1998

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.

BACKGROUND: Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial. METHODS: 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy. FINDINGS: Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg). INTERPRETATION: Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)

Blood Glucose↗
PubMed1999

Efficacy of indapamide in central diabetes insipidus.

BACKGROUND: Central diabetes insipidus (CDI) results from deficient vasopressin (antidiuretic hormone) secretion and causes polydipsia and polyuria. Desmopressin, a synthetic analog of vasopressin, is the drug of choice in the treatment of CDI, but in mild cases, there are alternative drugs that can be used, including chlorpropamide, carbamazepine, and thiazides. METHODS: In this study, we investigated the efficacy of treatment with indapamide, which is an antihypertensive diuretic oral agent, in 20 consecutive patients with CDI. The diagnosis of CDI was established by water-deprivation and vasopressin tests. Before the study, serum and urinary osmolality, daily urinary volume, and serum electrolyte levels were measured in all 20 patients. Indapamide (2.5 mg/d) was administered for 10 days, and then the investigations were performed again; for purposes of comparison, 250 mg/d of chlorpropamide was also administered to 11 of the 20 patients who had been given indapamide. RESULTS: Indapamide revealed a 40.56% +/- 9.70% (mean +/- SD) (range, 19.6%-55.0%) reduction in 24-hour urinary volume and an increase in urinary osmolality, as well as a decrease in serum osmolality, and was as effective as chlorpropamide (P<.05) in the treatment of CDI. CONCLUSION: Because of its low cost and lack of significant adverse effects, indapamide may be a suitable, easy-to-use alternative oral agent for some patients with CDI.

Adolescent↗
PubMed1998

UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent, 39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0 mmol l(-1), > or = 7.8 mmol l(-1) to < 10.0 mmol l(-1) and < 7.8 mmol l(-1) at randomization required additional therapy (p < 0.001). In the initial 3 years, non-obese subjects (BMI < 30 kg m(-2)) were more likely to require additional therapy than obese patients (BMI > or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype at presentation and perhaps on the agent used initially. Higher failure rates were found in those with higher glucose concentrations, those who were younger, those with lower beta-cell reserve and those randomized to glibenclamide compared with chlorpropamide.

Adult↗
PubMedDate not supplied

Factors moderating the effect of oral sulfonylureas on free water clearance.

The effects of the antidiuretic agent chlorpropamide and the diuretic agent tolazamide on solute-free water clearance (CH2O) were compared in noninsulin-dependent diabetic patients undergoing water diuresis. Hyperglycemia (fasting serum glucose above 200 mg/dl) obscured the effects of these two sulfonylureas on CH2O. Thiazide or ethacrynic acid enhancement of chlorpropamide antidiuresis was also blunted by hyperglycemia and attendant osmotic diuresis. Thus, the low incidence of symptomatic hyponatremia during chlorpropamide treatment of diabetic patients may be explained by persistent hyperglycemia in such patients.

Aged↗
PubMed1979

Diabetes: the genetic connections.

Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas--in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.

Chlorpropamide↗
PubMed2006

Depth profiling of compression-induced disorders and polymorphic transition on tablet surfaces with grazing incidence X-ray diffraction.

PURPOSE: The importance of induced crystal disorders like crystallite size, crystal defects, and amorphicity with respect to the dissolution rate of the drug has been discussed in many cases. Thus, the characterization of these properties is of great importance in the pharmaceutical formulation development, although the exact correlation between disorders and dissolution rate is still unclear. The aim of this study was to analyze pharmaceutical tablets with grazing incidence X-ray diffraction, which enables the depth profiling of the crystallographic properties of the tablets. To study and clarify the potential of grazing incidence diffraction in the analysis of pharmaceutical materials, the effect of the compaction process on the surface of tablets was examined. METHODS: Carbamazepine, tolbutamide, and chlorpropamide tablets, compacted using different compression pressures, were studied using grazing incidence angle X-ray diffraction. The effects of compression on the crystallographic properties were investigated as a function of the distance from the tablet surface. RESULTS: The surfaces of the tolbutamide and chlorpropamide tablets were disordered due to the compression. The manifestation of the disorder was deduced to be due to amorphicity, small crystallite size, and amount of crystal defects. The changes were mainly on the surface and diminished strongly as a function of the distance from the surface of the tablet. Moreover, the changes were dependent on the compression pressure used. The changes on the surface of the carbamazepine tablets were also due to the compression but these changes were not clearly dependent on the depth nor the compression pressure. The partial phase transition took place in the chlorpropamide tablets due to the compression. The magnitude of the transition was not highest on the surface because amorphization and texturization also took place on the tablet surface during the compression. CONCLUSIONS: The present study proved that grazing incidence X-ray diffraction is a potential novel research tool to reveal crystallographic transformations taking place on the surfaces of the tablets induced, for example, by compression pressure.

Carbamazepine↗
PubMed1981

The pharmacology of sulfonylureas.

In this report we review the pharmacology of the hypoglycemic sulfonylurea drugs. The early work with sulfonylureas is briefly described. The pharmacokinetics of first-generation sulfonylureas, such as tolbutamide, chlorpropamide, acetohexamide and tolazamide, are described. The first-generation sulfonylureas are compared with second-generation sulfonylureas such as glyburide, glipizide and glibornuride. These latter drugs have a more nonpolar or lipophilic side chain, which results in a marked increase in their hypoglycemic potency. Because of the low serum concentration required for effective therapy, it is necessary to measure the serum concentration of second-generation sulfonylureas by gas-liquid chromatography or radioimmunoassay. The second-generation sulfonylureas do not produce facial flushing after ethanol ingestion (Antabuse effect) and are not uricosuric. Glyburide (but not glipizide or glibornuride) has been evaluated for its effect on water excretion. Glyburide not only does not increase water retention but in fact also increases free water clearance. The second-generation sulfonylureas bind to human serum albumin by nonionic forces in contrast with tolbutamide and chlorpropamide which bind by ionic forces. Thus, anionic drugs such as phenylbutazone, warfarin and salicylate do not displace glyburide from albumin as they displace tolbutamide and chlorpropamide. Therefore, it may be safer to administer the second-generation sulfonylureas than the more polar sulfonylureas when concurrent administration of other pharmacologic agents is likely. The sulfonylurea drugs lower plasma glucose concentrations in diabetic patients by stimulating insulin secretion and by potentiating the biologic effect of the insulin on such tissues as skeletal muscle, fat and liver. The mechanism of the latter so-called extra-pancreatic effect may be activated by increasing the deficient numbers of insulin receptors on muscle, fat or liver cells.

Acetohexamide↗
PubMed1985

A case of chronic liver disease due to tolazamide.

Although chlorpropamide and tolbutamide are well recognized as causes of hepatotoxicity, there are only 3 reported cases of hepatic injury caused by a third oral hypoglycemic agent, tolazamide. In 2 of these cases, the liver-function tests returned to normal when the drug was discontinued. In the third case, the patient had cholestasis from chlorpropamide before administration of tolazamide and developed chronic liver disease. We are reporting the second instance of chronic liver disease induced by tolazamide. Our patient had been taking chlorpropamide, but she had no evidence of liver disease before administration of tolazamide. Tolazamide should be considered as a drug capable of producing hepatotoxicity that on occasion may be chronic.

Aged↗
PubMed2002

Coefficient of failure: a methodology for examining longitudinal beta-cell function in Type 2 diabetes.

AIMS: We describe a new method, the determination of the coefficient of failure, which allows the assessment of beta-cell failure from any index of glycaemia. Previous methods using glycaemic thresholds and calculating time-to-failure have systematic deficiencies relating to bias, reproducibility and statistical power. Analyses using threshold methodologies and conventional survival analysis have an intrinsic disadvantage in that they use categorical data and thus make no allowance for near-failure, or progression towards failure. In contrast, the coefficient of failure includes all data in the analysis and takes into account improvement of glycaemia as well as deterioration of glycaemia. METHODS: We describe the use of a 'coefficient of failure' defined as the slope of the least-squares regression line of a glycaemic index vs. time calculated for each individual patient on constant monotherapy. We exemplify the method using HbA1c levels from data from patients on chlorpropamide (n = 64) or glibenclamide (n = 65) monotherapy in the Oxford cohort of the UKPDS. RESULTS: Chlorpropamide-treated patients showed a mean coefficient of failure of 0.34 HbA(1c)%/year (0.44%/year sd) and glibenclamide-treated patients 0.50 HbA(1c)%/year (0.50%/year sd) (P = 0.046; unpaired two-tailed t-test). Kolmogorov-Smirnov testing demonstrated that the coefficients did not differ significantly from a normal distribution (chlorpropamide P = 0.12; glibenclamide P = 0.13). CONCLUSIONS: The coefficient of failure gives an estimate of beta-cell failure using any index of glycaemia. The coefficient is not constrained by predetermined glycaemic thresholds for failure and it allows the rate of decline in beta-cell function to be determined on any therapy or combination of therapies.

Chlorpropamide↗
PubMed2004

The advantages and disadvantages of a 'herbal' medicine in a patient with diabetes mellitus: a case report.

BACKGROUND: Patient-initiated alternative treatments in the management of chronic conditions are common and increasing in the United Kingdom. To date, there have been no reports of herbal medicine use alone in the management of diabetes mellitus. We report here the case of a man who attained excellent glycaemic control using a 'herbal' medicine and reveal how important it was to identify the products of active constituents. CASE REPORT: A 48-year-old man attending our clinic in Tooting, South London with known Type 2 diabetes, with evidence of both micro- and macro-vascular diabetes-related complications, was poorly controlled despite a drug regimen consisting of oral metformin and twice daily insulin. He went to India for at least 1 year and on returning to the clinic had excellent glycaemic control off all diabetic medication. While away he had started himself on a regimen of three different 'herbal' balls. Samples of blood were found to contain chlorpropamide in a therapeutic concentration; chlorpropamide was also found in one of the balls. He has been counselled on the potential risks associated with chlorpropamide and his treatment reverted to a more conventional treatment regimen. CONCLUSIONS: General practitioners and hospital physicians should be alert to those patients returning from abroad on effective 'herbal' medications that these may in fact contain an active ingredient.

Chlorpropamide↗
PubMed1979

Glycosylated haemoglobin concentrations in newly diagnosed diabetics before and during treatment.

Concentrations of total glycosylated haemoglobins (Hb A1) were measured in 40 diabetics at diagnosis and at monthly intervals after treatment with chlorpropamide, insulin, or diet alone was begun. The mean Hb A1 concentration at presentation in 16 patients treated with chlorpropamide was significantly higher than that in 12 patients treated with insulin, and the duration of glycaemic symptoms was much longer in the chlorpropamide-treated group. In contrast, the mean plasma glucose concentration was similar in both groups. The mean concentrations of Hb A1 and plasma glucose at diagnosis in the 12 patients treated by diet alone were lower than those in the other two groups, and most of these patients were free of symptoms. Treatment quickly relieved symptoms and lowered plasma glucose in all patients. The Hb A1 concentration fell significantly with treatment such that after two months there was no significant difference between the three groups, although results remained above the normal range. These findings support the theory that the Hb A1 concentration reflects the blood glucose control over the previous one to two months and suggest that the duration of hyperglycaemia may be important in determining the Hb A1 concentration as well as the absolute blood glucose concentration.

Adult↗
PubMed1972

Effect of oral hypoglycaemic agents on glucose tolerance in pancreatic diabetes.

The short-term therapeutic effect of oral hypoglycaemic agents has been assessed in 12 patients with symptomatic diabetes secondary to chronic pancreatitis (pancreatic diabetes). In six patients who had moderate to severe carbohydrate intolerance, associated with severe insulinopaenia during arginine infusion, the potent sulphonylurea chlorpropamide produced no change in the fasting blood glucose level after two weeks of treatment. This contrasted with the significant reduction produced in a matched group of maturity-onset primary diabetics. The six patients with milder diabetes, and a greater (although still subnormal) insulin secretory capacity, showed an improvement in oral glucose tolerance during the first hour following glucose administration while on chlorpropamide. When the biguanide phenformin was substituted for chlorpropamide in five of these patients, a statistically insignificant improvement in glucose tolerance was observed during treatment. Applications of these findings to the practical management of pancreatic diabetes are briefly considered.

Adult↗