Diabetic Glucose Tolerance Test Research Articles

HEPATIC NEUROPATHY

The peripheral nerve function was affected in 31 out of 34 patients with severe chronic hepatic failure, 20 of whom had a surgical portacaval shunt. Clinical findings were confined to the legs, an elevated vibratory perception threshold (VPT) on the big toe being the most common sign. However, the nerve function in the arm was also impaired. During ischaemia the rise in VPT (index finger) was delayed in 18 patients. An equivalent slowing of the sensory nerve conduction velocity was recorded in the digit-wrist and the wrist-elbow segments of the median nerve, accompanied by a reduction in amplitude and an increase in temporal dispersion of the action potentials. The sensory threshold for electrical stimuli (digit 3) was significantly raised. The frequency of neurological findings suggests that a peripheral nerve dysfunction is an integral part of the severe chronic hepatic failure syndrome. There was no relation to the routine liver function tests or to the galactose elimination capacity, a measure of the functioning liver mass. Neurological findings occurred with the same frequency in patients with and without chronic alcoholism or a diabetic glucose tolerance test. From the distribution of findings it is suggested that hepatic neuropathy results from a metabolic inhibition of the nerve axon membrane function.

Adaptive Closed-Loop Control Provides Blood-Glucose Regulation Using Dual Subcutaneous Insulin and Glucagon Infusion in Diabetic Swine

In order to stave off deleterious complications of the disease, the ultimate task for people with diabetes is to maintain their blood glucose in euglycemic range. Despite technological advancements, conventional open-loop therapy often results in prolonged hyperglycemia and episodic hypoglycemia, in addition to necessitating carbohydrate counting, frequent glucose monitoring, and drug administration. The logical conclusion in the evolution of exogenous insulin therapy is to develop an automated closed-loop control system. Eleven closed-loop control experiments were conducted in four anesthetized diabetic pigs, with carbohydrate loads simulated by intravenous glucose administration through ear-vein catheters. Type 1 diabetes-like pathology was induced using intravenous administration of cytotoxin streptozotocin. The augmented model-predictive control algorithm accounts for the accumulation of subcutaneous insulin, which is critical in avoiding excessive insulin dosing. Control results consistently showed successful blood-glucose regulation to euglycemic range within 80-120 minutes after intravenous glucose loads, with no incidence of hypoglycemia. This is consistent with a negative oral glucose tolerance test for diabetes and is the optimal postprandial regulation that can be achieved with subcutaneous insulin administration. Results also demonstrated the potency of subcutaneous glucagon in staving off episodic hypoglycemia and revealed efficacy of the control algorithm in coping with a twofold variation in subject weights, while simultaneously overlooking erratic blood-glucose fluctuations. Using an automated adaptive glucose-control system, we show successful blood-glucose regulation in vivo and establish, definitively, the plausibility and practicality of closed-loop blood-glucose control using subcutaneous insulin and glucagon infusion in type 1 diabetes. The control system strikes an intricate balance between tight blood-glucose control and optimal drug consumption, while simultaneously maintaining emphasis on simplicity and reliability.

Polyuria and polydipsia in an elderly population: Its relationship to previously undiagnosed diabetes

AbstractThis study aimed to find the prevalence of symptoms of diabetes, its relationship to previously undiagnosed diabetes within an elderly population, and its relationship to indices ofglycaemia within the diabetic subjects.It was designed as a cross‐sectional survey of the prevalence of previously undiagnosed diabetes, diagnosed by glucose tolerance test(GTT), and the prevalence ofpolyuria or polydipsia ascertained by questionnaire, in Melton Mowbray, Leicestershire, UK. All residents aged 65, 70, 75, 80 and 85 years, and spouses who were alive, willing, and not known to have diabetes, had a glucose tolerance test; 1 in 5 of all subjects and all subjects with possible diabetic GTT were asked if they had polyuria or polydipsia. All subjects with diabetic GTT had indices of glycaemic level measured. Diabetes mellitus was defined by 1985 WHO criteria, and symptoms ofpolyuria and/or polydipsia classified as present or absent. In diabetic subjects glycated haemoglobin level, fructosamine level and glycosuria were recorded.Of 24 elderly subjects found to have previously undiagnosed diabetes during the Melton diabetes survey, only seven hadpolyuria/polydipsia. Of 210 subjects with normal glucose tolerance, five had symptoms. Of 20 subjects with impaired glucose tolerance, none had symptoms. In the subjects found to be diabetic, symptoms were not related to presence/absence of glycosuria, diuretic use or indices ofglycaemia. Seventeen of the diabetic subjects were aged 78 years or less and these included all seven symptomatic subjects.Both the British and American Diabetes Associations' public awareness campaigns stress the presence of symptoms of diabetes as reasons to consult a physician. Previous studies have suggested that these symptoms are common in subjects with newly diagnosed diabetes. However, polyuria and polydipsia are uncommon in the elderly with undiagnosed diabetes and are extremely unlikely in octogenarians; otherwise there is no overt reason why individual diabetic subjects may or may not get polyuria/polydipsia. Public awareness campaigns should emphasize that absence of symptoms does not exclude diabetes.

Workshop Report: Treating Diabetes and its Complications

RESEARCH OPPORTUNITIES— The work group discussed research opportunities in biomedical, behavioral, and health service research on some of the complications of NIDDM. The panel chose to focus on aspects of the prevention of blindness, nephropathy, heart disease, and amputations, and aspects of gestational diabetes and diabetes in pregnancy. The panel agreed at the onset that the best treatment of diabetes and its complications was prevention of diabetes by treating early abnormalities of glucose tolerance or impaired glucose tolerance. Primary prevention of diabetes may be achieved by treating such abnormalities by diet, exercise, or oral hypoglycemic agents. Alternatively, treatment of the earliest abnormalities of NIDDM, such as a diabetic glucose tolerance test, early in the natural history of diabetes might also be effective. These topics were discussed in more detail in the work group on the Prevention and Early Treatment of NIDDM.

EFFECT OF HEAVY DRINKING AND ALCOHOL WITHFRAWAL ON MARKERS OF CARBOHYDRATE METABOLISM

A number of biochemical markers were monitored in 38 male alcoholic patients at admittance and one week later. In patients with a drinking period of greater than 3 weeks the median fasting B-glucose decreased significantly as well as S-fructosamine concentrations. The ability of S-fructosamine to identify patients with a diabetic glucose tolerance test, expressed in terms of sensitivity and specificity, was 12 and 47%, respectively; that of HbA1c was still lower.

Accuracy of Reported Family History of Diabetes Mellitus: Results From San Luis Valley Diabetes Study

There are two possible sources of bias in the assessment of family history of diabetes: 1) a person with diabetes may be more likely to report a diabetic relative than a nondiabetic person would be, and 2) relatives of individuals with diabetes may be more likely to be tested for diabetes than relatives of nondiabetic individuals. We conducted a study on a subsample of families of subjects in the San Luis Valley Diabetes Study to examine these issues. A sample of 5 White and 5 Hispanic subjects (probands) with diabetic glucose tolerance tests and the same number with normal glucose tolerance were selected. The 20 probands all provided contact information on their 227 primary family members. Ninety-two percent of the family members had interviews completed by themselves or, if deceased, by surrogates other than the proband. Family members were asked by telephone if they had ever been tested for diabetes, when they had been most recently tested, why they had been tested, and if they had ever been told they had diabetes. The results showed that study subjects accurately reported family history of diabetes, because there were no discrepancies between proband and family reports. A positive family history of diabetes was associated with increased reported screening in Hispanics, but a similar effect in White families was not seen. Women were also more likely to report being screened than men regardless of whether there was a positive family history of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic exocrine and endocrine function after subtotalpancreatectomy for nesidioblastosis

Pancreatic exocrine and endocrine function was assessed in seven patients 1 to 2 years after 95% pancreatectomy (group A) and three patients 9 to 11 years after 75% pancreatectomy (group B). In all cases surgery was undertaken for the treatment of hyperinsulinism and the histologic diagnosis was nesidioblastosis. The activities of pancreatic enzymes and bicarbonate concentrations were generally normal in group B, but were reduced in approximately half the children in group A. One child in group A had significant exocrine failure and poor weight gain. Blood glucose levels and fasting insulin levels were normal during a standard glucose tolerance test in all of the group B patients. One had a low fasting blood glucose level. In the group A patients three had low fasting glucose levels and one a frankly diabetic glucose tolerance test. C peptide and insulin levels were comparable but inappropriate insulin levels were noted in one patient, suggesting that the control of glucose-stimulated insulin release may remain abnormal. The results suggest that pancreatic function is not seriously impaired in the majority of patients 1 to 2 years after 95% pancreatectomy and that it is comparable to that noted in 75% pancreatectomy patients followed over a longer period of time.

Glucose tolerance test and glycosylated haemoglobin measurement for diagnosis of diabetes mellitus--an assessment of the criteria of the WHO Expert Committee on Diabetes Mellitus 1980.

Fasting glycosylated haemoglobin was analysed in 535 consecutive patients having an oral 75 g glucose tolerance test for diagnostic purposes. A reference range for fasting glycosylated haemoglobin was established from patients with a non-diabetic glucose tolerance test as defined by the World Health Organisation Expert Committee on Diabetes Mellitus. The predictive value of a glycosylated haemoglobin of over 10.0% (mean normal +/- 3 SD) for detecting a diabetic glucose tolerance test was 89% but sensitivity was only 43%. A raised glycosylated haemoglobin is useful for confirming the diagnosis of diabetes mellitus in patients with long-standing hyperglycaemia but glycosylated haemoglobin is within the reference range in many patients with newly developed diabetes or other minor abnormalities of glucose tolerance. The glucose tolerance test must remain the test of choice in these patients.

Glycosylated hemoglobin in the diagnosis of non-insulin-dependent diabetes mellitus.

Fifty-one patients aged over 35 yr were referred because of glycosuria for a glucose tolerance test (GTT). In each patient hemoglobin A1 (HbA1) was estimated by a commercial minicolumn method and compared with hemoglobin A1c (HbA1c) determined by a modification of the method of Trivelli et al. Both HbA1 and HbA1c levels were normal in 96% of those patients with normal GTTs. In patients with diabetic GTTs, HbA1 was elevated in 90% but HbA1c was raised in only 43%. HbA1 estimation is a useful screening test for non-insulin-dependent diabetes and should be considered when criteria for diagnosis of diabetes mellitus are discussed.

Metabolic investigations in Menière's disease.

This paper presents the results of various metabolic investigations in patients with Menière's disease. It is a follow-up article on the preliminary findings of the study which was published in this Journal recently (Moffat et al., 1979). Fifty patients (29 male, and 21 female) with Menière's disease conforming to the criteria set out by the Committee of Hearing and Equilibration of the American Academy of Ophthalmology and Otolaryngology (1972) were involved. The incidence of abnormal metabolic states was no higher than that of a comparable group in the general population. One of the patients had a diabetic glucose tolerance test curve, four had lag curves. One patient had a high TSH level and was clinically myxoedematous. Three patients (two male, and one female) had primary hyperlipidaemia and one female patient had hyperlipidaemia secondary to myxoedema. There was no significant difference in response to intradermal pin prick skin tests compared with a controlled group.

Glycohemoglobin

In 140 persons with a normal glucose tolerance test (GTT), the median glycohemoglobin (GHb) level was 8.1% (95% limits, 6.5% to 9.0%). The GHb level was not significantly different in 30 patients with impaired GTT (8.6%). In all 14 patients with diabetic GTT and fasting plasma glucose (PG) level above 140 mg/dL, GHb level was above 10% (median, 11.3%). Of 25 patients with diabetic GTT but without fasting hyperglycemia, only two had GHb levels 10% or above. The GHb level correlated with the mean daily PG level in both 176 insulin-dependent (r_S, +.530) and 107 non-insulin-dependent (r_S, +.734) diabetics. Correlation was almost zero between GHb level and mean one-day PG level in 14 most brittle insulin-dependent diabetics. However, in them, there was a strong correlation (r_S, +.763) between GHb level and the mean of 20 or more PG values for the preceding month. Follow-up of 100 diabetics showed strong correlation (r_S, +.845) between the changes in GHb level and in the mean PG level. Decrease of the mean PG level of 100 mg/dL was accompanied by a drop of the GHb level of about 2%. (<i>Arch Intern Med</i>1981;141:747-749)

Glycohemoglobin. Its use in the follow-up of diabetes and diagnosis of glucose intolerance.

In 140 persons with a normal glucose tolerance test (GTT), the median glycohemoglobin (GHb) level was 8.1% (95% limits, 6.5% to 9.0%). The GHb level was not significantly different in 30 patients with impaired GTT (8.6%). In all 14 patients with diabetic GTT and fasting plasma glucose (PG) level above 140 mg/dL, GHb level was above 10% (median, 11.3%). Of 25 patients with diabetic GTT but without fasting hyperglycemia, only two had GHb levels 10% or above. The GHb level correlated with the mean daily PG level in both 176 insulin-dependent (rs, +.530) and 107 non-insulin-dependent (rs, +.734) diabetics. Correlation was almost zero between GHb level and mean one-day PG level in 14 most brittle insulin-dependent diabetics. However, in them, there was a strong correlation (rs, +.763) between GHb level and the mean of 20 or more PG values for the preceding month. Follow-up of 100 diabetics showed strong correlation (rs, +.845) between the changes in GHb level and in the mea PG level. Decrease of the mean PG level of 100 mg/dL was accompanied by a drop of the GHb level of about 2%.

Congenital lipodystrophy: An endocrine study in three siblings

Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...

Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease.

Neuropathological studies of Huntington's disease reveal neuronal atrophy, lipofuscin accumulation and other findings characteristic of the aged brain, although the onset of disease is only the fourth decade. The pathology is limited to specific areas such as the caudate nucleus, cerebral cortex and hypothalamus. 14 patients with documented Huntington's disease (mean age of 44.4 years with a range of 27-79 years) were studied by oral glucose tolerance tests (GTT) and intravenous arginine tolerance tests performed under standardized metabolic conditions. Seven of the 14 patients had impaired carbohydrate tolerance. Mean plasma glucose level at 2h was 90.4+/-6.2 mg/100 ml in the patients with a normal GTT and 148.1+/-8.9 mg/100 ml in the patients with a diabetic type GTT. Mean peak insulin level in the nondiabetic group occurred at 1/2 h and was 60.2+/-10.1 muU/ml, but in the diabetic group the peak insulin level occurred at 2h and was 155.9+/-33.8 mgU/ml. There was failure of suppression of growth hormone during the GTT, with a rise to abnormally high levels at 5h (18.6+/-5.6 ng/ml). Arginine infusion resulted in normal glucose and insulin rise in the nondiabetic patients with Huntington's disease. However, arginine infusion provoked an elevated insulin response in those with a diabetic GTT, and an exaggerated growth hormone response in the majority of the patients. It is uncertain whether these observations are related to abnormal cerebral aging per se, direct hypothalamic neuronal degeneration, or perhaps a relative imbalance of intracerebral neurotransmitters including dopamine.

PANCREATIC ISLET-CELL ANTIBODY AS A MARKER FOR ASYMPTOMATIC AND LATENT DIABETES AND PREDIABETES

Pancreatic islet-cell antibodies (I.C.Ab) were detected in 31 patients with organ-specific autoimmune disorders, 4 first-degree relatives of I.C.Ab-positive diabetics, and 1 apparently normal subject, none of whom had clinical evidence of diabetes. 10 of these 36 subjects were found to have diabetic glucose-tolerance tests (G.T.T.S), 4 had lag storage, and 22 had normal G.T.T.S. 2 had latent diabetes, as evidenced by diabetic G.T.T.S during pregnancy and thyrotoxicosis; another 2 subsequently developed insulin-dependent diabetes (I.D.D.). Serum from 26 subjects had been stored for 1-11 yr before the G.T.T.S were done. The titres in some were shown to rise and fall over the years, while in others they remained remarkably constant. There was no correlation between the titre, change in titre or the duration of I.C.Ab or the presence of HLA-B8, BW15, or CW3 and the result of the G.T.T. In addition to acting as a marker for asymptomatic and latent diabetes and prediabetes, it seems that the presence of I.C.Ab in the serum may define a new group of potential diabetics with normal G.T.T.S. Many such subjects have one or more organ-specific autoimmune disorders (irrespective of diabetic family history), but some are first-degree relatives of I.C.Ab-positive subjects (mainly I.D.D.). About 0·5% of the general population also have I.C.Ab in their serum.

Ten-year follow-up report on Birmingham Diabetes Survey of 1961. Report by the Birmingham Diabetes Survey Working Party.

In a diabetes survey in 1960-1, 808 patients from a whole-practice population who either had glycosuria or were used as age- and sex-matched controls were given a 50-g oral glucose tolerance test (GTT). Ten years later the test was repeated in 382 cases. Of the original group, 126 had died and a similar number refused the second test. The original GTT results were classed as normal or as showing GTT diabetes, lag storage, renal glycosuria, or miscellaneous abnormalities. Most of those who converted to florid diabetes came from the GTT diabetes group, all the remainder having shown another minor degree of abnormality in the test; 23% with GTT diabetes, however, remained unchanged, while 32% returned to normal or had only minor anomalies. Of the original lag-storage group 57% remained unchanged or became normal, though 24% had converted to a diabetic abnormality. Renal glycosuria was an innocent peculiarity. The various miscellaneous abnormalities tended to change and showed an excessive conversion to diabetes. There was no accelerating trend towards diabetes in the second five years of follow-up. Those who developed florid diabetes showed an excess mortality comparable to that of clinical diabetics in general. Those who remained normal had the lowest mortality, while those with minor abnormalities occupied an intermediate position.

Gastric inhibitory polypeptide (GIP) in chronic pancreatitis.

The plasma gastric inhibitory polypeptide (GIP), pancreatic glucagon-like immunoreactivity (PGLI), and gut glucagon-like immunoreactivity (GGLI) responses to oral glucose have been measured in five patients with chronic pancreatitis (with diabetic glucose tolerance tests) and in matched nondiabetic controls. Plasma GIP levels rise rapidly after glucose ingestion before changes in circulating glucose and insulin concentration. Patients with pancreatitis have a greater than normal GIP response to oral glucose, which may account for the relatively unimparied insulin response to oral glucose in these patients compared with that to iv glucose, as has been previously found. Patients with pancreatitis also have a paradoxical rise in PGLI and an exaggerated rise in GGLI concentration following oral glucose.

Endocrinopathy in thalassaemia major.

Pituitary, adrenal, and pancreatic functions were investigated in 9 patients with thalassaemia major. 9 a.m. plasma ACTH values were 148-480 pg/ml (normal range 15-70 pg/ml). Cortisol and growth hormone response to insulin-induced hypoglycaemia was normal in all. 24-hour urinary excretions of 17-ketosteroids and 17-hydroxycorticosteroids were normal. There was normal cortisol response to intramuscular injection of ACTH. In a physiological adrenal stimulation test there was a significantly smaller response to each physiological dose of tetracosactrin. 4 patients had diabetic glucose tolerance tests--none are clinically diabetic. The mean plasma glucose utilization constant (Kgl=2-02) is significantly smaller than normal. Plasma insulin response both in the oral and the intravenous glucose tolerance test was significantly smaller than normal. The data were consistent with severe and widespread impairment of endocrine function and a plausible explanation would be iron deposition in endocrine organs. It is suggested that pituitary hyperfunction of ACTH secretion is due to target organ unresponsiveness which can be shown in its early stages only by a physiological test of the adrenal cortex. Skin pigmentation in thalassaemia seems to be due to the melanophore-stimulating effect of this raised plasma ACTH.

Studies of glucose tolerance, insulin and growth hormone secretion during the menstrual cycle in healthy women.

ORAL glucose tolerance tests were performed at regular intervals during the menstrual cycle in 33 healthy women. When the results were adjusted for the point in cycle at which the tests were done, minor variations in glucose tolerance were observed during the cycle. At no stage was a diabetic glucose tolerance test encountered. A small variation in serum insulin levels was noted also. Growth hormone levels did not vary significantly. The most striking feature of the study was the high incidence of low blood sugar levels found at 90 to 120 minutes after glucose ingestion.

Carbohydrate homeostasis and pancreatic islet cell funtion in thalassemia.

Glucose tolerance and pancreatic alpha and beta cell functions were evaluated in eight thalassemic patients, from 5 to 31 years old, receiving chronic transfusion therapy. Two patients had insulin-dependent diabetes, and two had a diabetic glucose tolerance test; one patient had a blood glucose response compatible with reactive hypoglycemia. All but two patients had a delayed or diminished insulin response, or both, to glucose infusion. In seven of eight patients the glucagon response to infusion of alanine was significantly reduced. Abnormalities of carbohydrate homeostasis are frequently seen in regularly transfused thalassemic patients. In such patients iron overload often results in diminished alpha and beta cell function.