Beta cell function in long term NIDDM (type 2) patients and its relation to treatment

Pancreatic beta cell function was assessed by estimation of fasting and post prandial plasma C-peptide in 183 non-insulin dependent diabetic patients, who were treated with oral hypoglycaemic drugs, for more than 10 years. One-hundred-and-forty-one patients, continued to respond to oral hypoglycaemic agents (Group I) and in 42 the control was not satisfactory and had to be changed over to insulin (secondary failure, Group II). Significant beta cell reserve (PP CP greater than or equal to 0.6 pmol/ml) was present in 89 out of 183 patients (48%) and 83 (93%) of them responded to oral hypoglycaemic agents. Among the 94 patients with low beta cell reserve, 58 (62%) were on oral hypoglycaemic agents and the other 36 (38%) were on insulin. Of the 42 patients with secondary failure to the oral drugs, 36 (86%) had low C-peptide while 6 (14%) had significant C-peptide values. Secondary failure to oral hypoglycaemic agents can also occur in spite of good beta cell reserve. Beta cell reserve was not correlated either to the duration of diabetes or the age at diagnosis of the patients.     

Obesity in type 2 diabetes: prevalence, treatment trends and dilemmas

This retrospective observational study investigated the prevalence of obesity in persons with type 2 diabetes, trends in obesity resulting from the duration and treatment of diabetes, and treatment-related changes in HbA1c and body mass index (BMI). Data on 1773 type 2 diabetics (802 men and 971 women) were obtained from the CroDiabNET registry. Follow-up included the analysis of patients' age, disease duration, diabetes treatment, BMI and HbA1c values. A significantly higher rate of overweight and obesity was found in persons with type 2 diabetes as compared to the general population. A significant decrease in BMI was observed in the groups treated by diet, and in those treated by oral hypoglycaemic agents (p < 0.05), regardless of their pharmacotherapeutic group, in contrast to a significant increase in BMI observed in the groups treated with insulin (alone or in combination with oral hypoglycaemic agents) (p < 0.05). Persons with type 2 diabetes lost weight only during the first years of the disease, while with diabetes duration and insulin treatment they regained weight. A significant increase in HbA1c was observed in the groups treated with sulfonylureas (p < 0.05), whereas all other groups revealed either a significant decrease (p < 0.05) or no change in HbA1c. Our findings suggest the necessity of an integrated approach to managing type 2 diabetic patients that would simultaneously address both diabetes and obesity. Good glycaemic control is imperative and diabetes treatment should not be postponed. Because of a possible concomitant weight gain, aggressive weight control measures should be applied concurrently in order to achieve maximum treatment benefit.     

Some parameters of hemostasis in diabetic patients

Parameters of blood coagulation and fibrinolysis in diabetic patients chronically treated with oral hypoglycaemic agents and insulin have been analysed. All examined patients were divided into four subgroups: I-treated with biguanides, II-treated with sulfonylurea derivatives, III-sulfonylurea and biguanide derivatives simultaneously, IV-treated with insulin. Observed decrease in haemostasis parameters and activation of fibrinolysis in patients treated with only biguanides seemed associated with favourable effect of these agents on the decrease in the risk of the thrombotic complications in diabetes mellitus.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

The effects of oral agent or insulin treatments on the plasma lipoproteins and the plasma lipoprotein lipase activator in diabetic patients

The structure and the metabolism of plasma lipoproteins are altered in diabetes mellitus. Insulin or oral agent treatments affect the lipoprotein metabolism in addition to improving hyperglycemia. However, it is not clear whether the alterations seen in lipoproteins during treatment are related to the degree of diabetic control or to the mode of diabetic treatment. The effects of insulin or oral agent treatments on the plasma lipoproteins and lipoprotein lipase activator were compared in a strictly defined non-obese, non-insulin dependent diabetic patient. Both treatment groups had similar plasma triglyceride, total cholesterol, low and high density lipoprotein cholesterol, and lipoprotein lipase activator levels. Lipoprotein lipase activator contents of the very low density lipoproteins correlated positively with their triglyceride (r = 0.803 in insulin, r = 0.828 in oral agent treated patients) and protein (r = 0.713 in insulin, r = 0.862 in oral agent treated patients) contents. The findings of this study indicated that plasma lipid levels, very low density lipoprotein compositions, and lipoprotein lipase activator contents were not significantly different in non-obese, non-insulin dependent diabetic patients treated with either oral hypoglycemic agents or insulin.     

Prevalence and clinical characteristics of diabetic peripheral neuropathy in hospital patients with Type 2 diabetes in Korea

Diabet. Med. 29, e290-e296 (2012) ABSTRACT: Aims Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type?2 diabetic mellitus treated at hospitals in Korea. Methods Questionnaires and medical records were used to collect data on 4000 patients with Type?2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. Results The prevalence of neuropathy was 33.5% (n?=?1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. Conclusion There was a high prevalence of peripheral neuropathy in patients with Type?2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.     

Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction.

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).     

Diabetes registers: a grassroots approach.

OBJECTIVES--To compile a register of diabetic patients within the catchment area of a district general hospital and evaluate the characteristics of the population using aggregated data from a general practice audit. DESIGN--Cross sectional study. Practices identified all known diabetics and completed a questionnaire from information in each patient''s medical record. SETTING--Practices affiliated to a district audit group in south east England. MAIN OUTCOME MEASURES--Number of participating practices; prevalence of diabetes and its complications; and sex distribution of patients, age at diagnosis and review, treatment, and metabolic control. Comparisons with similar data from other studies. RESULTS--41 out of 43 practices participated, and 2574 diabetic patients were identified (prevalence 1.18%). 52.4% of patients were male. The mean age was 61.6 years. 32% of patients were treated with insulin, 51.5% with oral hypoglycaemic agents, 16.5% with diet alone. The mean random blood glucose concentration was 10.4 mmol/l and glycosylated haemoglobin 10.1%. 8% had proteinuria, 7% a history of myocardial infarction, 5% a history of stroke, and 2% a diabetes related amputation. These proportions were not significantly different from those found in studies performed by different methods in Poole, Islington, Powys, Trowbridge, and Southall. CONCLUSION--It is feasible to compile a register of diabetic patients in a district and evaluate their characteristics by using only general practice sources.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

What happens to defaulters from a diabetic clinic?

The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4.1% overall and 3.5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic. Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p less than 0.05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p less than 0.02) and higher haemoglobin A1 (HbA1) concentrations (11.7% v 8.4%; p less than 0.01). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p less than 0.05) and a greater incidence of new retinopathy (p less than 0.02), which correlated with their higher diastolic blood pressures (p less than 0.01) and HbA1 concentration (p less than 0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p less than 0.05). Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic.     

Risk of severe hypoglycaemia in insulin treated diabetic patients transferred to human insulin: a case control study.

OBJECTIVE--To examine whether transfer from animal insulin to human insulin is associated with an increased risk of severe hypoglycaemia. DESIGN--Matched case-control study of insulin treated diabetic patients admitted to hospital because of hypoglycaemia during 1984-7, the period when human insulin was introduced into treatment. SETTING--Case admissions and control admissions were obtained from eight public hospitals within the Swiss canton of Berne and a second control group comprised members of the Bernese section of the Swiss Diabetes Association. SUBJECTS--94 patients with insulin treated diabetes with a total of 112 admissions for hypoglycaemia during 1984-7 (case admissions), 182 patients with insulin treated diabetes seen in the same hospitals for reasons other than hypoglycaemia with a total of 225 admissions (control admissions), and 86 insulin treated diabetic patients who were members of the Bernese section of the Swiss Diabetes Association. MAIN OUTCOME MEASURES--Type of insulin used at time of admission, glycaemic control as measured by amount of glycated haemoglobin or glucose concentration; severity of hypoglycaemia. RESULTS--Treatment with human insulin at admission was more common in cases than controls (52/112 (46%) admissions v 77/225 (34%); p = 0.003). 116 out of 129 (90%) of admissions taking human insulin had been transferred from animal insulin, mainly because of non-availability of porcine insulins. The ratio of rate of hypoglycaemia in those taking human insulin to the rate in those taking animal insulin was 2.4 (95% confidence interval 1.3 to 4.4). Other risk factors for hypoglycaemia were a history of hypoglycaemic coma (rate ratio of history to no history 3.8, 2.3 to 6.4) and good glycaemic control (rate ratio of good to poor control 3.9, 1.4 to 7.5). With multivariate analysis the increase in rate ratio associated with use of human insulin rose to 3.0 (1.4 to 6.4). Comparison with the diabetes association controls also showed an increased risk associated with use of human insulin (2.2; 1.1 to 4.8). CONCLUSIONS--Transfer of treatment from animal insulin to human insulin was associated with an increased risk of severe hypoglycaemia. Caution should be exercised when transferring diabetic patients to human insulin. Further studies are required to elucidate why this effect occurs.     

Metabolic control of diabetes in general practice clinics: comparison with a hospital clinic.

An assessment was made of the degree of metabolic control achieved in diabetic patients attending mini clinics run by general practitioners compared with that in matched diabetic patients attending a hospital clinic. Patients were grouped according to whether they were being treated with diet alone, an oral hypoglycaemic, insulin once daily, or insulin twice daily. Statistical analysis showed no significant difference between patients attending mini clinics and those attending the hospital clinic in retrospective mean blood glucose, retrospective mean glycosylated haemoglobin (HbA1), or prospective HbA1 concentrations. General practitioners providing diabetic care on an organised basis can achieve a degree of glycaemic control in diabetic patients equal to that reached by a hospital clinic.     

Double blind clinical and laboratory study of hypoglycaemia with human and porcine insulin in diabetic patients reporting hypoglycaemia unawareness after transferring to human insulin.

OBJECTIVES--To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin. DESIGN--Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin. SETTING--Clinical investigation unit of teaching hospital recruiting from diabetes clinics of five teaching hospitals and one district general hospital. SUBJECTS--17 patients with insulin dependent diabetes mellitus of more than five years'' duration who had reported altered hypoglycaemia awareness within three months of transferring to human insulin. MAIN OUTCOME MEASURES--Glycaemic control and frequency of hypoglycaemic episodes during two months'' treatment with each insulin. Glucose thresholds for physiological and symptomatic responses during clamping. RESULTS--Glycaemic control did not change with either insulin. 136 hypoglycaemic episodes (eight severe) were reported with human insulin and 149 (nine severe) with porcine insulin (95% confidence interval -4 to 2.5, p = 0.63). 20 episodes of biochemical hypoglycaemia occurred with human insulin versus 18 with porcine insulin (-0.8 to 1, p = 0.78). During controlled hypoglycaemia the mean adrenaline response was 138 nmol/l/240 min for both insulins; neurohormonal responses were triggered at 3.0 (SE 0.2) versus 3.1 (0.2) mmol/l of glucose for adrenaline and 2.5 (0.1) versus 2.5 (0.1) mmol/l for subjective awareness. CONCLUSIONS--These data suggest that human insulin per se does not affect the presentation of hypoglycaemia or the neurohumoral, symptomatic, and cognitive function responses to hypoglycaemia in insulin dependent diabetic patients with a history of hypoglycaemia unawareness.     

Effect of β-Caryophyllene on insulin resistance in skeletal muscle of high fat diet and fructose-induced type-2 diabetic rats

High fat diet feeding results in hyperglycemia and insulin resistance, which is a major pathological feature of type-2 diabetes mellitus. The use of oral hypoglycaemic drugs is limited due to its deleterious side effects and there is a need to find more efficacious agents for diabetes management. Hence, it is of interest to show the mechanism of action of β-Caryophyllene on insulin signalling molecules in gastrocnemius muscle of high fat diet - induced type-2 diabetic rats. An oral effective dose of with β-Caryophyllene (200 mg/kg b.wt) was given for 30 days to high fat diet (comprising 2% cholesterol, 1% cholic acid, 30% coconut oil, 67% conventional rat feed) and fructose fed type-2 diabetic rats to find out whether β-Caryophyllene regulates IRS-1/Akt pathway of insulin signalling. The data shows that, β-Caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) in diabetic rats whereas there is no significant difference in mRNA expression of insulin receptor-substrate-1 (IRS-1) was observed among groups. The Akt mRNAand GLUT-4mRNA and protein level were also improved in gastrocnemius muscle of type-2 diabetic rats. Thus, we concluded that β-Caryophyllene could be used as potential phyto medicine for type-2 diabetes management.     

The diabetic day-care unit. I. Development of an index to evaluate diabetes control.

In order to measure the effect of a diabetic day-care unit on diabetes control two scoring scales were constructed, one for insulin-dependent diabetics and the other for patients managed by diet or oral agents or both. Both scales were based on observations of blood and urine glucose concentrations, ketonuria, symptoms of diabetes and deviation from ideal weight. The scale for insulin-dependent diabetics also included the frequency and severity of insulin reactions and frequency of hospital admission for acidosis. Scores for 45 insulin-dependent patients and for 55 diabetics treated by diet with or without oral agents in the unit indicated significant improvement in diabetes control in both groups.     

14-Year Risk of All-Cause Mortality According to Hypoglycaemic Drug Exposure in a General Population

Purpose

Guidelines for management of patients with type 2 diabetes mellitus recommend the use of hypoglycaemic drugs when lifestyle interventions remain insufficient for glycaemic control. Recent trials have provided worrying safety data on certain hypoglycaemic drugs. The aim of this study was to assess 14-year risk of all-cause mortality according to hypoglycaemic drug exposure at baseline, in a general population.

Methods

Our analysis was based on the observational Third French MONICA survey on cardiovascular risk factors (1995–1997). Vital status was obtained 14 years after inclusion, and assessment of determinants of mortality was based on multivariable Cox modelling.

Results

There were 3336 participants and 248 deaths over the 14-year period. At baseline, there were 3162 (95%) non-diabetic, 46 (1%) untreated type 2 diabetic and 128 (4%) type 2 diabetic subjects with hypoglycaemic drug treatment (metformin alone (31%), sulfonylureas alone or in combination (49%), insulin alone or in combination (10%), or other treatments (9%)). After adjustment for duration of diabetes, history of diabetes complications, area of residence (centre), age, gender, educational level, alcohol consumption, smoking, blood pressure, LDL and HDL cholesterol, which all were significant and independent determinants of mortality, the hazard ratio for all-cause mortality was 3.22 [95% confidence interval: 0.87–11.9] for untreated diabetic subjects, 2.28 [0.98–5.26] for diabetics treated with metformin alone, 1.70 [0.92–3.16] for diabetics with sulfonylureas and 4.92 [1.70–14.3] for diabetic with insulin versus non-diabetic subjects.

Conclusions

Our results support the conclusion that until more evidence is provided from randomized trials, a prudent approach should be to restrain use of insulin to situations in which combinations of non-insulin agents have failed to appropriately achieve glycemic control, as it is recommended in the current guidelines for the management of type 2 diabetes.     

Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus

Twenty-two hypertensive diabetic patients were admitted to a double-blind, within-patient study, and treated with propranolol 80 mg and metoprolol 100 mg twice daily for 4 weeks according to a cross-over design. Dosages of the two drugs such as to induce comparable cardiovascular effects, did not induce relevant changes of fasting blood glucose levels in patients receiving the oral hypoglycaemic agent glibenclamide (group 1), insulin (group 2) or diet alone (group 3). Glucose tolerance, assessed with a 75 g oral load, was however decreased by propranolol, and not by metoprolol in the glibenclamide-treated group. Glucose-induced insulin secretion was reduced by propranolol and not by metoprolol both in the group treated by diet alone and in the glibenclamide-treated group. It is concluded that cardioselective metoprolol seems to be more suitable than the non-selective propranolol in the treatment of arterial hypertension in diabetic subjects, particularly when sulfonylureas are being used as hypoglycaemic agents.     

Correlation between Serum Electrolytes and Fasting Glucose and Hb1Ac in Saudi Diabetic Patients

In subjects with impaired insulin action, alterations of the serum sodium and potassium concentrations have been reported. The resulting cationic imbalance, along with the osmotic effect of the elevated sugar levels, could influence the course of diabetes mellitus management. Therefore, this study was conducted to compare the fasting blood glucose and HbA1c levels with those of the serum electrolytes. Blood samples were collected for assessment of HbA1c, fasting blood glucose (FBS), and electrolytes using different automated methods. A significant association between the serum sodium and FBS levels among types 1 and 2 insulin-treated patients, and type 2 oral agent patients was observed. A total of 138 diabetic subjects were randomly selected from any gender aged between 25 and 65?years at the University Diabetes Center, King Saud University, Riyadh KSA. The subjects were classified into types 1 or 2 DM using ADA criteria. Blood samples were collected for assessment of HbA1c, FBS, and electrolytes using different automated methods. It showed a significant association between serum sodium, FBS among type 1, type 2 insulin treated, and type 2 oral agent groups. However, the association of sodium and HbA1c was insignificant when analyzed individually. A statistically significant association (P?相似文献   

Anti-diabetic and anti-oxidant effects of Zingiber Officinale on alloxan-induced and insulin-resistant diabetic male rats

This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic and insulin resistant diabetic rats. The experimental rats exhibited hyperglycaemia accompanied with weight loss to confirm their diabetic state. Ginger effectively reduced fasting blood glucose and malonydealdehyde levels in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. Furthermore, ginger increased serum insulin level and also enhanced insulin sensitivity in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. The results of the study clearly show that dietary ginger has hypoglycaemic effect, enhances insulin synthesis in male rats and has high antioxidant activity. One of the likely mechanisms is the action of malonydealdehyde, which acts as a scavenger of oxygen radicals. Keywords: Diabetes mellitus, Insulin resistance, Zingiber officinale, Malonydealdehyde.     

Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.

OBJECTIVE--To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN--Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING--One routine diabetic unit in a university teaching hospital. PATIENTS--23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES--Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS--There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS--Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.