Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke

BACKGROUND: Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents. METHODS: Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L). RESULTS: Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT. CONCLUSIONS: Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.     

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V

Aims

To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method.

Materials and methods

This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets.

Results

Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia.

Conclusions

Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.     

Association of sleep time with diabetes mellitus and impaired glucose tolerance

BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index. RESULTS: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded. CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.     

Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin response to glucose

Summary In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin-dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45–74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20 % glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150–180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 5 min, 5 to 15 min, > 15 min; p < 0.05). The split-proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests. [Diabetologia (1999) 42: 177–180] Received: 5 June 1998 and in final revised form: 5 October 1998     

New criteria for interpretation of the 75 g oral glucose tolerance test in pregnancy

A 75 g oral glucose tolerance test (OGTT) was performed on 135 high-risk pregnant patients. When the current World Health Organization (WHO) criteria for the diagnosis of gestational-glucose tolerance were applied, 88 patients were considered normal, 11 had gestational diabetes, and 36 patients had impaired-glucose tolerance, respectively. The plasma glucose, insulin, and C-peptide levels during the OGTT were further studied in the 88 patients (who had normal results). Two metabolically distinct groups were identified; a group (n = 53) with a 2-hour plasma glucose less than or equal to 6.6 mmol/L (118.8 mg/dL), had a normal insulin and C-peptide pattern, and a second group (n = 35) who had 2-hour plasma glucose greater than 6.6 mmol/L displayed a glycemic, insulin, and C-peptide pattern similar to that of patients with gestational diabetes mellitus. The risks of macrosomic babies and operative delivery were significantly greater in the latter group. These results suggest that in our pregnant population, a group of patients with impaired glucose tolerance will be under-diagnosed using the current WHO criteria. Based on our results new criteria for gestational glucose intolerance are suggested for our population.     

Can HbA1c and One-Hour Glucose Concentration in Standard OGTT Be Used for Evaluation of Glucose Homeostasis in Childhood?

Objective: To investigate whether glycosylated hemoglobin (HbA1c) and 1-hour glucose level in oral glucose tolerance test (OGTT) are useful parameters for evaluation of glucose homeostasis in childhood.Methods: The medical records of 106 obese/overweight children aged from 7 to 18 years who underwent OGTT were evaluated retrospectively. The subjects were divided into 2 groups according to their one-hour glucose concentration. Group 1 consisted of subjects whose one-hour glucose level was <155 mg/dL, and Group 2 consisted of subjects whose one-hour glucose level was ≥155mg/dL. The fasting and 2-hour glucose concentrations of the groups werecompared. The sensitivity and specificity levels were determined using the ROC curve to assess the predictive value of HbA1c for impaired glucose tolerance (IGT).Results: The mean 2-hour glucose concentration of the subjects in Group 2 was significantly higher than that of the subjects in Group 1 (137.8±35.5 mg/dL versus 113.1±21.2 mg/dL, p<0.05). If a 5.5% cut-off value for HbA1c was accepted as predictor of IGT, the sensitivity was 63% and specificity was 70%. 31% of the subjects with HbA1c levels at or above 5.5% had IGT. This rate was significantly lower in subjects who had HbA1c levels below 5.5% (p<0.05).Conclusions: Obese/overweight children and adolescents whose 1-hourglucose level is ≥155 mg/dL in the standard OGTT carry a high risk for IGT. Obese/overweight children and adolescents whose HbA1c level is at or above 5.5% may have IGT even though their fasting glucose level is normal, thus, OGTT is necessary to evaluate the glucose tolerance.Conflict of interest:None declared.     

Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive ?-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes

Background:Elevated fasting intact proinsulin is a biomarker of late-stage ß-cell-dysfunction associated with clinically relevant insulin resistance. In this pilot investigation, we explored the potential value of measuring intact proinsulin as a functional predictor of ß-cell exhaustion during an oral glucose tolerance test (OGTT).Methods:The study was performed with 31 participants, 11 of whom were healthy subjects (7 female, age: 59 ± 20 years), 10 had impaired glucose tolerance (IGT, 6 female, 62 ± 10 years), and 10 had known type 2 diabetes (T2DM, 5 female, 53 ± 11 years, HbA1c: 7.0 ± 0.6%, disease duration: 8 ± 5 years). During OGTT, blood was drawn after 0 hours, 1 hour, and 2 hours for determination of glucose and intact proinsulin. Five years later, patients were again contacted to assess their diabetes status and the association to the previous OGTT results was analyzed.Results:The OGTT (0 hours/1 hour/2 hours) results were as follows: healthy subjects: glucose: 94 ± 8 mg/dL/140 ± 29 mg/dL/90 ± 24 mg/dL, intact proinsulin: 3 ± 2 pmol/L/10 ± 7 pmol/L/10 ± 5 pmol/L); IGT: glucose: 102 ± 9 mg/dL/158 ± 57 mg/dL/149 ± 34 mg/dL, intact proinsulin: 7 ± 4 pmol/L/23 ± 8 pmol/L/28 ± 6 pmol/L; T2DM: glucose: 121 ± 20 mg/dL/230 ± 51 mg/dL/213 ± 34 mg/dL; intact proinsulin: 7 ± 7 pmol/L/26 ± 9 pmol/L/27 ± 10 pmol/L). Five years later, all of the IGT and 2 of the healthy subjects had developed T2DM and one had devloped IGT. All of them had elevated 2-hour proinsulin values in the initial OGTT, while patients with normal intact proinsulin results did not develop diabetes.Conclusions:Elevated 2-hour intact proinsulin levels during OGTT were predictive for later type 2 diabetes development. Further studies need to confirm our findings in larger populations.     

Proposed guidelines for screening of hyperglycemia in patients hospitalized with COVID-19 in low resource settings

Background and aimsThe coronavirus disease 2019 (COVID-19) pandemic has immensely strained healthcare systems worldwide. Diabetes has emerged as a major comorbidity in a large proportion of patients infected with COVID-19 and is associated with poor health outcomes. We aim to provide a practical guidance on screening of hyperglycemia in persons without known diabetes in low resource settings.MethodsWe reviewed the available guidelines on this subject and proposed an algorithm based on simple measures of blood glucose (BG) which can be implemented by healthcare workers with lesser expertise in low resource settings.ResultsWe propose that every hospitalized patient with COVID-19 infection undergo a paired capillary BG assessment (pre-meal and 2-h post-meal). Patients with pre-meal BG < 7.8 mmol/L (140 mg/dL) and post-meal BG < 10.0 mmol/L (180 mg/dL) may not merit further monitoring. On the other hand, those with one or more value above these thresholds should undergo capillary BG monitoring (pre-meals and 2 hours after dinner) for the next 24 hours. When two or more (≥50%) such values are significantly elevated [pre-meal ≥8.3 mmol/L (150 mg/dL) and post-meal ≥11.1 mmol/L (200 mg/dL)], pharmacotherapy should be immediately initiated. On the other hand, in patients with modest elevation of one or more values [pre-meal 7.8–8.3 mmol/L (140–150 mg/dL) and post-meal 10.0–11.1 mmol/L (180–200 mg/dL)], dietary modifications should be initiated and pharmacotherapy considered only if BG control remains suboptimal.ConclusionWe highlight strategies for screening of hyperglycemia in persons without known diabetes treated for COVID-19 infection in low resource settings. This guidance may well be applied to other settings in the near future.     

Diagnostic and therapeutic implications of relationships between fasting, 2-hour postchallenge plasma glucose and hemoglobin a1c values

BACKGROUND: Increased fasting plasma glucose (FPG) and 2-hour postchallenge plasma glucose (PCPG) levels with normal hemoglobin A1c (HbA1c) levels are recognized as risk factors for cardiovascular disease. We undertook this study to determine the relationships between FPG and 2-hour PCPG levels over the normal HbA1c range and to assess the need to control FPG and 2-hour PCPG levels to achieve HbA1c targets recommended by the American Diabetes Association (ADA), International Diabetes Federation (IDF), and American College of Endocrinology (ACE). METHODS: The data of all healthy individuals with HbA1c values less than 7.0% (N = 457) who underwent oral glucose tolerance tests between 1986 and 2002 for either screening as potential research volunteers (93%) or diagnostic purposes (7%) were analyzed. RESULTS: Of 404 individuals with normal HbA1c levels (<6.0%), 60% had normal glucose tolerance, 33% had impaired glucose tolerance, 1% had isolated impaired FPG, and 6% had type 2 diabetes mellitus. Of 161 individuals without normal glucose tolerance, 80% had normal FPG levels. Both FPG and 2-hour PCPG levels increased as HbA1c increased and were significantly correlated (r = 0.63, P<.001), but the 2-hour PCPG level increased at a rate 4 times greater than FPG and accounted for a greater proportion of HbA1c. People who met the IDF and ACE HbA1c targets (<6.5%) had significantly lower 2-hour PCPG levels than those who met the ADA target (<7.0%) (P =.03), whereas FPG levels were similar. CONCLUSIONS: Most individuals with HbA1c values between 6.0% and 7.0% have normal FPG levels but abnormal 2-hour PCPG levels, suggesting that an upper limit of normal for FPG at 110 mg/dL (6.11 mmol/L) is too high and that attempts to lower HbA1c in these individuals will require treatment preferentially directed at lowering postprandial glucose levels.     

Relationship of elevated casual blood glucose level with coronary heart disease, cardiovascular disease and all-cause mortality in a representative sample of the Japanese population. NIPPON DATA80

Aims/hypothesis High fasting blood glucose is one of the well-known risk factors for CHD. However, in certain settings, patients cannot always be expected to fast. For example, community screenings for cardiovascular disease (CVD) risk factors in Japan are performed under non-fasting conditions to achieve high participation rates. Thus, we examined a representative cohort of the Japanese population (n = 9,444, follow-up period 17.3 years) to clarify whether high casual blood glucose (CBG) can predict CVD mortality. Methods We defined CBG groups as follows: high CBG ≥ 11.1 mmol/l or participants with a history of diabetes mellitus; borderline high, 7.77 ≤ CBG < 11.1 mmol/l; higher normal, 5.22 ≤ CBG < 7.77 mmol/l); and lower normal, CBG < 5.22 mmol/l. The multivariate-adjusted hazard ratios (HRs) for CHD, CVD and all-cause mortality were calculated. Results The crude CHD mortality rate was 0.84 per 1,000 person-years. Age- and sex-adjusted HRs for CHD mortality were high among participants with CBG levels  ≥ 7.77 mmol/l, regardless of time since last meal. Multivariate-adjusted HRs (95% CI) of CHD mortality in high and borderline high CBG groups were 2.62 (1.46–4.67) and 2.43 (1.29–4.58), respectively. Similar results were observed for both CVD and all-cause mortality. Even within the normal blood glucose range, each 1 mmol/l increase in CBG was associated with a statistically significant increase in the HR for CVD mortality (1.12, 95% CI 1.02–1.22). Population-attributable fractions of the combined groups of high and borderline high CBG for CHD, CVD and all-cause mortality were 12.0, 4.9 and 3.5%, respectively. Conclusions/interpretation Increases in CBG, even within the normal range, predict CVD mortality. Electronic supplementary material The online version of this article (doi:) contains a full list of the NIPPON DATA research group members, which is available to authorised users.     

Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus

BACKGROUND: High admission blood glucose levels after acute myocardial infarction (AMI) are common and associated with an increased risk of death in subjects with and without known diabetes. Recent data indicate a high prevalence of abnormal glucose metabolism in patients with unknown diabetes at the time of AMI. We investigated the predictive value of admission blood glucose levels after AMI for long-term prognosis in patients with and without previously diagnosed diabetes mellitus, particularly in those with unknown diabetes but with blood glucose levels in the diabetic range. METHODS: In a retrospective study with prospective follow-up, 846 patients (737 without and 109 with known diabetes) were eligible for follow-up during a median of 50 months (range, 0-93 months). RESULTS: During follow-up, 208 nondiabetic patients (28.2%) and 47 diabetic patients (43.1%) died (P =.002). An increase of 18 mg/dL (1 mmol/L) in glucose level was associated with a 4% increase of mortality risk in nondiabetic patients and 5% in diabetic patients (both P<.05). Of the 737 previously nondiabetic subjects, 101 had admission blood glucose levels of 200 mg/dL (11.1 mmol/L) or more, and mortality in these patients was comparable to that in patients who had established diabetes (42.6% vs 43.1%). CONCLUSIONS: Admission blood glucose level after AMI is an independent predictor of long-term mortality in patients with and without known diabetes. Subjects with unknown diabetes and admission glucose levels of 200 mg/dL (11.1 mmol/L) or more after AMI have mortality rates comparable to those of subjects with established diabetes. Admission blood glucose level may serve to identify subjects at high long-term mortality risk, in particular among those with unknown diabetes.     

Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea

BACKGROUND: Sleep-disordered breathing (SDB) is a prevalent condition associated with significant comorbidities, including hypertension, obesity, cardiovascular disease, and insulin resistance. It has been previously shown that the severity of insulin resistance is related to the severity of SDB. METHODS: Using a 72-hour continuous glucose monitoring system, we studied changes in interstitial glucose levels and measured hemoglobin A1c levels in 25 patients with type 2 diabetes mellitus before and after continuous positive airway pressure (CPAP) treatment for SDB. RESULTS: With a mean +/- SD CPAP treatment period of 83 +/- 50 days, the mean +/- SD 1-hour postprandial glucose values were significantly reduced for breakfast (191 +/- 68 mg/dL to 130 +/- 41 mg/dL [10.6 +/- 3.8 mmol/L to 7.2 +/- 2.3 mmol/L]), lunch (196 +/- 70 mg/dL to 138 +/- 49 mg/dL [10.9 +/- 3.9 mmol/L to 7.7 +/- 2.7 mmol/L]), and dinner (199 +/- 66 mg/dL to 137 +/- 48 mg/dL [11.0 +/- 3.7 mmol/L to 7.6 +/- 2.7 mmol/L]). In the 17 patients with a baseline hemoglobin A1c level greater than 7%, there was a significant reduction in hemoglobin A1c level (9.2% +/- 2.0% to 8.6% +/- 1.8%). Furthermore, in subjects who used CPAP for more than 4 h/d, the reduction in hemoglobin A1c level was significantly correlated with days of CPAP use. There was no such correlation in subjects who used CPAP for 4 h/d or less. CONCLUSIONS: These findings suggest that SDB is pathophysiologically related to impaired glucose homeostasis, and that CPAP can be an important therapeutic approach for diabetic patients with SDB.     

Assessment of the new criteria for diabetes mellitus according to 10-year relative survival rates

Summary The validity of the new diagnostic criteria for diabetes mellitus for Japanese subjects was assessed by the long-term prognosis of 501 patients, found in an epidemiological survey of 6,681 people in a Japanese town. Ten-year relative survival rates were examined in relation to the 50 g oral glucose tolerance test (serum glucose determined by a ferricyanide method). Subjects were classified using the new criteria. The prognosis of normal subjects (fasting glucose <140 mg/dl (7.8 mmol/l) and 2-hour glucose level <140 mg/dl) and of subjects with fasting glucose <140 mg/dl and 2-h 140–200 mg/dl (7.8–11.1 mmol/l) did not differ from that of the general population. Diabetics (fasting140 mg/dl and 2-h200 mg/dl) showed a significantly reduced survival rate, corresponding to an excess mortality. Subjects with a fasting level <140mg/dl and 2-h 200mg/dl had a relative survival rate similar to that of normal subjects. As a group, fasting levels l40 mg/dl indicated a reduced survival rate, regardless of the 2-h level, while those with a 2-h level 200 mg/dl alone failed to show a significantly reduced survival rate. Thus, the fasting glucose values appeared to be more closely related to death rate than the 2-hour glucose values.     

Evaluation of Reference Metrics for Continuous Glucose Monitoring in Persons Without Diabetes and Prediabetes

Background:Recent guidelines have been developed for continuous glucose monitoring (CGM) metrics in persons with diabetes. To understand what glucose profiles should be judged as normal in clinical practice and glucose-lowering trials, we examined the glucose profile of healthy individuals using CGM.Methods:Persons without diabetes or prediabetes were included after passing a normal oral glucose tolerance test, two-hour value <8.9 mmol/L (160 mg/dL), fasting glucose <6.1 mmol/L (110 mg/dL), and HbA1c <6.0% (<42 mmol/mol). CGM metrics were evaluated using the Dexcom G4 Platinum.Results:In total, 60 persons were included, mean age was 43.0 years, 70.0% were women, mean HbA1c was 5.3% (34 mmol/mol), and mean body mass index was 25.7 kg/m². Median and mean percent times in hypoglycemia <3.9 mmol/L (70 mg/dL) were 1.6% (IQR 0.6-3.2), and 3.2% (95% CI 2.0; 4.3), respectively. For glucose levels <3.0 mmol/L (54 mg/dL), the corresponding estimates were 0.0% (IQR 0.0-0.4) and 0.5% (95% CI 0.2; 0.8). Median and mean time-in-range (3.9-10.0 mmol/L [70-180 mg/dL]) was 97.3% (IQR 95.4-98.7) and 95.4% (95% CI 94.0; 96.8), respectively. Median and mean standard deviations were 1.04 mmol/L (IQR 0.92-1.29) and 1.15 mmol/L (95% CI 1.05; 1.24), respectively. Measures of glycemic variability (standard deviation, coefficient of variation, mean amplitude of glycemic excursions) were significantly greater during daytime compared with nighttime, whereas others did not differ.Conclusions:People without prediabetes or diabetes show a non-negligible % time in hypoglycemia, median 1.6% and mean 3.2%, which needs to be accounted for in clinical practice and glucose-lowering trials. Glycemic variability measures differ day and night in this population.     

Family history of diabetes in middle-aged Swedish men is a gender unrelated factor which associates with insulinopenia in newly diagnosed diabetic subjects

Summary We have investigated the association of a family history of diabetes with glucose tolerance in a population of Swedish men. All men 35–54 years of age in 1992 and living in four different local municipalities of the outer Stockholm area were screened by questionnaire. From 10 236 completed questionnaires 1622 men, selected for presence of such a history but without known diabetes, as well as 1507 men without a family history underwent an oral glucose tolerance test. Diabetes (2 h-plasma glucose levels > 11.0 mmol/l) was detected in 55 and impaired glucose tolerance (plasma glucose levels 7.8–11.0 mmol/l) in 172 subjects. The odds ratio of diabetes, associated with a family history, was 4.1, confidence interval 2.1–8.3 and for impaired glucose tolerance 1.6, confidence interval 1.2–2.3. Influence of a family history was measurable also within the range of normal 2-h glucose concentrations: compared to 2-h glucose levels < 3.8 mmol/l; the odds ratio associated with a family history was 1.4, confidence interval 1.1–1.7 and 1.3, confidence interval 1.1–1.6 for concentrations 4.8–5.7 mmol/l and 5.8–7.7 mmol/l respectively. The odds ratio of diabetes and impaired glucose tolerance among men with a family history increased with number and closeness of relatives with diabetes but was not affected by the gender of the family member. Overweight (BMI > 25.0 kg/m²) increased the odds ratio of diabetes in subjects with a family history, the odds ratio being 24, confidence interval 3–177, when both conditions were present. In subjects with Type II (non-insulin-dependent) diabetes mellitus discovered during the investigation, the presence of a family history of diabetes was associated with decreased insulin secretion rather than insulin resistance as assessed by fasting insulin, homeostasis model assessment, and the 2-h insulin response to the oral glucose tolerance test. We conclude that a family history of diabetes strongly but independently of gender associates with decreased glucose tolerance. Furthermore, the results are compatible with a major role for low insulin secretion in the diabetogenic influence of a family history of diabetes in middle-aged Swedish men. Lastly, the very high risk for diabetes in middle-aged men with both a family history of diabetes and obesity indicates that such people should, for the purpose of therapeutic intervention, be identified in the general population. [Diabetologia (1999) 42: 15–23] Received: 9 March 1998 and in revised form: 1 July 1998     

Involvement of low adiponectin levels in impaired glucose tolerance

To investigate the association between serum adiponectin levels and 2-hour post-75-g oral glucose load glycemia, we conducted 75-g oral glucose tolerance tests in 50 subjects who had been diagnosed as having impaired glucose tolerance (IGT) within the prior 3 years. When adjusted for age, body mass index, and sex, serum adiponectin levels in the IGT and diabetes mellitus groups were significantly lower than those in the normal glucose tolerance and impaired fasting glucose groups (P < .0001). To determine which variables had significant impacts on 2-hour post-oral glucose glycemia, we performed multiple regression analyses. In stepwise analysis, serum adiponectin levels showed the highest F value (F = 6.43), suggesting the adiponectin level to be an independent predictor of 2-hour post-oral glucose glycemia. Thus, our clinical data suggest the involvement of low adiponectin levels in IGT and diabetes mellitus. To further assess this possibility, we prepared mice fed a high-fat diet for 2 months as an IGT model. Afterward, we compared the 2-hour postglucose glycemia in the IGT mice overexpressing recombinant adiponectin with that in control IGT mice. Mice overexpressing adiponectin showed significantly blunted 2-hour postglucose glycemia (5.66 ± 0.39 mmol/L) as compared with control mice (8.52 ± 0.67 mmol/L), whereas fasting glycemia was not significantly altered by adiponectin overexpression. Taken together, our results reveal the plasma glucose level in response to a glucose load to be negatively associated with serum adiponectin levels, suggesting low adiponectin levels to be one of the predictors of abnormal glucose homeostasis in IGT.     

Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria

Aims/hypothesis We investigated relations between fasting blood glucose and the incidence of cancer.Methods A population-based cohort of more than 140,000 Austrian adults (63,585 men, 77,228 women) was followed over an average of 8.4 years. Incident cancer (other than non-melanoma skin cancers) was ascertained by a population-based cancer registry (n=5,212). Cox proportional-hazards models were used to estimate hazard rate ratios (HR) stratified for age and adjusted for smoking, occupational group and body mass index.Results The highest fasting blood glucose category (≥7.0 mmol/l) was weakly associated with all cancers combined (HR 1.20; 95% CI, 1.03–1.39 in men and 1.28; 95% CI, 1.08–1.53 in women) relative to the reference level (4.2–5.2 mmol/l). The strongest association was found for liver cancer in men (HR 4.58; 95% CI, 1.81–11.62). Positive associations between fasting hyperglycaemia (6.1–6.9 or ≥7.0 mmol/l) and cancer incidence were also observed for non-Hodgkin’s lymphoma in men, and for colorectal and bladder cancer in women. Breast cancer in women diagnosed at or after age 65 was also associated with fasting blood glucose ≥7.0 mmol/l. Positive associations with glucose values >5.3 mmol/l were noted for thyroid cancer, gallbladder/bile duct cancer and multiple myeloma in men and women combined.Conclusions/interpretation These findings provide further evidence that elevated blood glucose is associated with the incidence of several types of cancer in men and women.     

Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality

Abstract Aims/hypothesis. The aim of this study was to examine the possible link between isolated post-challenge hyperglycaemia (2-h post-challenge plasma glucose ≥ 11.1 mmol/l, and fasting plasma glucose < 7.0 mmol/l) and mortality. Methods. The data from three population based longitudinal studies (in Mauritius, Fiji and Nauru) were pooled and mortality rates were determined in 9179 people who were followed for between 5 and 12 years. Results. There were 595 people with previously diagnosed diabetes, and 799 with newly diagnosed diabetes, of whom 243 (31) had isolated post-challenge hyperglycaemia. In comparison with people without diabetes, people with isolated post-challenge hyperglycaemia had an increased risk of all-cause mortality [Cox proportional hazards ratio (95 % CI): 2.7 (1.8–3.9) – men; 2.0 (1.3–3.3) – women], and of cardiovascular mortality [2.3 (1.2–4.2) – men; 2.6 (1.3–5.1) – women]. In addition, men with isolated post-challenge hyperglycaemia had a high risk of cancer death [8.0 (3.6–17.9)]. Conclusion/interpretation. These data show that isolated post-challenge hyperglycaemia, which can only be identified by the 2-h glucose, is common, and at least doubles the mortality risk. This should be considered in the design of screening programmes that use only fasting glucose [Diabetologia (1999) 42: 1050–1054] Received: 18 March 1999 and in revised form: 27 May 1999     

Tests of glycemia for the diagnosis of type 2 diabetes mellitus

This paper discusses tests of glycemia for the diagnosis of type 2 diabetes mellitus, with particular reference to the 1997 diagnostic criteria of the American Diabetes Association. The potential benefits of the lower diagnostic threshold for fasting plasma glucose are not well defined. However, the change in the diagnostic cut-off for diabetes mellitus affects as many as 1.9 million persons in the United States; therefore, the medical and social costs of the lower threshold may be considerable. Type 2 diabetes mellitus is defined by a threshold imposed on the continuous distribution of glycemic levels, typically with respect to risk for microvascular complications. However, the burden of type 2 diabetes relates more to macrovascular than microvascular complications. Because no clear threshold exists for macrovascular complications, a formal balancing of direct and indirect costs with both microvascular and macrovascular complications may be appropriate to establish glycemic thresholds. Because fasting plasma glucose, hemoglobin A1c, and the oral glucose tolerance test all predict diabetic complications yet test reliability is better for fasting plasma glucose and hemoglobin A1c than for the oral glucose tolerance test, we suggest an alternative diagnostic approach: If random plasma glucose is elevated (> or =11.1 mmol/L [200 mg/dL]) and the hemoglobin A1c level is more than 2 SDs above the laboratory mean, then diabetes mellitus should be diagnosed, and management should be based on the hemoglobin A1c level. If the result of only one of these tests is positive, then fasting plasma glucose should be tested to evaluate the patient for impaired fasting glucose and diabetes mellitus. The glycemic threshold for type 2 diabetes should be established by cost-effectiveness analysis. The clinical diagnosis of diabetes mellitus could be streamlined by incorporation of hemoglobin A1c into established criteria.     

Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients

In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) compared with previous treatment with benzbromarone; and (2) investigate the combination therapy allopurinol–probenecid as an effective alternative treatment compared with previous benzbromarone treatment. A prospective, open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal. Patients were given 200–300 mg allopurinol (stage 1). When allopurinol failed to attain the target serum urate (sUr) levels ≤0.30 mmol/l, probenecid 1,000 mg/day was added (stage 2). Treatment with benzbromarone monotherapy (range: 100–200 mg/day; mean 138 mg/day) resulted in 92% of patients reaching target levels sUr ≤ 0.30 mmol/l with a decrease of 61[11]% compared to baseline. In stage 1, 32 patients completed treatment with allopurinol monotherapy (range 200–300 mg/day; mean 256 mg/day), which resulted in 25% of patients attaining sUr target levels. Decrease in sUr levels was 36[11]%, which was significantly less compared to treatment with benzbromarone (p < 0.001). In stage 2, 14 patients received allopurinol–probenecid combination therapy, which resulted in 86% of patients attaining target sUr levels (after failure on allopurinol monotherapy), which was comparable to previous treatment with benzbromarone (p = 0.81). Decrease in sUr levels was 53[9]% (CI 95%: 48–58%), which was a non-significant difference compared to previous treatment with benzbromarone (p = 0.23). Benzbromarone is a very effective antihyperuricemic drug with 91% success in attainment of target sUr levels ≤0.30 mmol/l. Allopurinol 200–300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels (13% success). In patients failing on allopurinol monotherapy, the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels (86% success).