Early lifestyle intervention in patients with non-insulin-dependent diabetes mellitus and impaired glucose tolerance

Some adult cleft palate patients show severe maxillary transverse contraction and posterior crossbite. This case report demonstrates successful surgical-orthodontic treatment of such a patient. Surgically assisted rapid maxillary expansion (SA-RME) was completed prior to comprehensive orthodontic treatment. The osteotomy was performed on both the buccal and lingual aspects of the posterior maxillary alveolus. A Hyrax-type maxillary-expansion appliance was used, and the screw (0.2 mm, one quarter turn) was turned two or three times per day. Comprehensive orthodontic treatment was initiated after extraction of the mandibular first premolars and four third molars. The maxillary lateral incisors were also extracted after active orthodontic treatment. The amount of expansion achieved using SA-RME was greater at the posterior than at the anterior maxilla. Midpalatal suture opening occurred. After orthodontic treatment, occlusal stability was satisfactory. This case demonstrates the effectiveness of SA-RME in adult cleft palate patients with severe posterior crossbite.     

Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients

The DNA sequences of two related plasmids pPR1 and pPR3 described previously in Streptococcus pneumoniae isolates from Germany and Spain were now determined. Both plasmids belong to a family of rolling circle (RC) plasmids found in a variety of bacteria. Their GC content with 32% is lower than that of the S. pneumoniae chromosomal DNA. The plasmid pPR3 has a molecular size of 3160 bp with four putative open reading frames, whereas pPR1 contained a deletion of 313 bp that included the 5'-part of ORF2 and upstream regions and differed by three bp from pPR3. The predicted protein of ORF1 showed high similarity to replication proteins of RC plasmids with 74% identical amino acids to RepA of Streptococcus thermophilus plasmids. Sequences similar to the plus origin of replication of ssDNA plasmids were present in both plasmids. They also contained a 152-bp region with over 83% identity to the minus origin of replication of the Streptococcus agalacticae plasmid pMV158.     

Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus

We examined the ability of an equivalent increase in circulating glucose concentrations to inhibit endogenous glucose production (EGP) and to stimulate glucose metabolism in patients with Type 2 diabetes mellitus (DM2). Somatostatin was infused in the presence of basal replacements of glucoregulatory hormones and plasma glucose was maintained either at 90 or 180 mg/dl. Overnight low-dose insulin was used to normalize the plasma glucose levels in DM2 before initiation of the study protocol. In the presence of identical and constant plasma insulin, glucagon, and growth hormone concentrations, a doubling of the plasma glucose levels inhibited EGP by 42% and stimulated peripheral glucose uptake by 69% in nondiabetic subjects. However, the same increment in the plasma glucose concentrations failed to lower EGP, and stimulated glucose uptake by only 49% in patients with DM2. The rate of glucose infusion required to maintain the same hyperglycemic plateau was 58% lower in DM2 than in nondiabetic individuals. Despite diminished rates of total glucose uptake during hyperglycemia, the ability of glucose per se (at basal insulin) to stimulate whole body glycogen synthesis (glucose uptake minus glycolysis) was comparable in DM2 and in nondiabetic subjects. To examine the mechanisms responsible for the lack of inhibition of EGP by hyperglycemia in DM2 we also assessed the rates of total glucose output (TGO), i.e., flux through glucose-6-phosphatase, and the rate of glucose cycling in a subgroup of the study subjects. In the nondiabetic group, hyperglycemia inhibited TGO by 35%, while glucose cycling did not change significantly. In DM2, neither TGO or glucose cycling was affected by hyperglycemia. The lack of increase in glucose cycling in the face of a doubling in circulating glucose concentrations suggested that hyperglycemia at basal insulin inhibits glucose-6-phosphatase activity in vivo. Conversely, the lack of increase in glucose cycling in the presence of hyperglycemia and unchanged TGO suggest that the increase in the plasma glucose concentration failed to enhance the flux through glucokinase in DM2. In summary, both lack of inhibition of EGP and diminished stimulation of glucose uptake contribute to impaired glucose effectiveness in DM2. The abilities of glucose at basal insulin to both increase the flux through glucokinase and to inhibit the flux through glucose-6-phosphatase are impaired in DM2. Conversely, glycogen synthesis is exquisitely sensitive to changes in plasma glucose in patients with DM2.     

The potential for lifestyle change to influence the progression of impaired glucose tolerance to non-insulin-dependent diabetes mellitus

Impaired glucose tolerance (IGT) is well recognized as a risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Detecting IGT offers a unique opportunity for targeting intervention to reduce the incidence of NIDDM. This article reviews current evidence for the efficacy of lifestyle intervention programmes involving people with IGT.     

Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance

OBJECTIVE: Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based study RESEARCH DESIGN AND METHODS: The population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information. CONCLUSIONS: The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.     

A high biotin diet improves the impaired glucose tolerance of long-term spontaneously hyperglycemic rats with non-insulin-dependent diabetes mellitus

Event-related potentials (ERPs) were recorded in a continuous memory recognition task. Readable non-words and abstract geometric figures were presented in an alternating manner with an inter-stimulus interval of 2.1 s. Probability of item repetition was 0.25, a lag of one item lay between initial presentation and repetition. OLD/NEW distinction was indicated by the subject's motor response. Using linked-mastoid electrodes for reference, material-specific hemispheric asymmetries of ERPs started 150 ms after stimulus onset in temporo-lateral and parietal recordings with ERPs elicited by non-words being lateralized to the left and those by figures to the right. Clear OLD/NEW ERP effects were found with non-words: Starting about 200-250 ms after stimulus presentation, ERPs of formerly presented (OLD) items were more positive-going in recordings over the midline than ERPs of items that were new and to be repeated (NEW). In contrast, no local OLD/NEW ERP-difference was found with figures. In some brain regions, OLD/NEW ERP-differences were larger over the left hemisphere compared to the right. This finding, however, did not differ between non-words and figures.     

Cardiovascular risk factors prior to the development of non-insulin-dependent diabetes mellitus in persons with impaired glucose tolerance: the Hoorn Study

The aim of the study was to analyze cardiovascular risk factors as predictors for developing non-insulin-dependent diabetes mellitus (NIDDM) in people with impaired glucose tolerance. A cross-sectional survey of glucose tolerance was conducted in people, aged 50-74, who were randomly selected from the registry of the middle-sized town Hoorn (The Netherlands). Based on the mean values of two oral glucose tolerance tests, people were classified in glucose tolerance categories according to the WHO criteria. The mean follow-up time was 36 months (range 13-55 months). The cumulative incidence of NIDDM was 34% (95% CI 16.9-45.1). In multiple logistic regression analysis, cardiovascular risk factors at baseline did not predict the conversion from impaired glucose tolerance to NIDDM, in contrast with the two-hour plasma glucose level (odds ratio 3.56, p < 0.001) and the fasting proinsulin level, as one of the determinants of beta-cell dysfunction (Odds ratio 2.1, p < 0.05). The baseline HDL-cholesterol level, one of the components of the insulin resistance syndrome, was associated with the conversion from impaired glucose tolerance to normal glucose tolerance (Odds ratio 1.58, p < 0.05). The results of our study seem to support the hypothesis that conversion from impaired glucose tolerance to normal glucose tolerance depends on insulin resistance and the development of NIDDM from impaired glucose tolerance depends on beta-cell dysfunction.     

Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group

OBJECTIVE: To assemble standardized estimates of abnormal glucose tolerance in adults in diverse communities worldwide and provide guidelines for the derivation of comparable estimates in future epidemiological studies. RESEARCH DESIGN AND METHODS: The project was limited to population-based investigations that had used current WHO criteria for diagnosis and classification of abnormal glucose tolerance. Raw data were obtained by WHO from surveys conducted during 1976-1991 of over 150,000 persons from 75 communities in 32 countries. Data within the truncated age range of 30-64 yr were adjusted to the standard world population of Segi. Age-specific prevalences also are reported for selected populations. RESULTS: Within the chosen age range, diabetes was absent or rare (< 3%) in some traditional communities in developing countries. In European populations, age-standardized prevalence varied from 3 to 10%. Some Arab, migrant Asian Indian, Chinese, and Hispanic American populations were at higher risk with prevalences of 14-20%. The highest prevalences were found in the Nauruans (41%) and the Pima/Papago Indians (50%). Age-standardized prevalence of IGT was low (< 3%) in some Chinese, traditional American Indian, and Pacific island populations. Moderate (3-10%) or high (11-20%) prevalences of IGT were observed in many populations worldwide. The highest estimates for prevalence of IGT were seen in female Muslim Asian Indians in Tanzania (32%) and in urban male Micronesians in Kiribati (28%). Prevalence of diabetes rose with age in all populations in which age-specific data were examined. This trend was most pronounced in those at moderate to high risk. The ratio of prevalence of diabetes in men versus women varied markedly between populations with little discernable trend, although IGT was generally more common in women. In most communities, at least 20% of diabetes cases were unknown before the survey, and in many communities, > 50% were previously undiagnosed. In both Chinese and Indian migrant populations, relative prevalence was high when compared with indigenous communities. CONCLUSIONS: Diabetes in adults is now a global health problem, and populations of developing countries, minority groups, and disadvantaged communities in industrialized countries now face the greatest risk.     

Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women

Small molecular weight calcium salts, if absorbed intact, could provide a nutritional source of calcium in subjects with impaired absorption of calcium by the saturable pathway. An understanding of the mechanism of absorption of calcium oxalate (as a representative salt) may be important nutritionally and therapeutically. The aim of the present study was to develop models to study absorption, distribution and retention of calcium and oxalate in rats as a basis for studying calcium oxalate absorption. Labeled compounds (45Ca and [14C]-oxalic acid) were administered to separate groups of rats orally (n = 8-11) or intravenously (n = 3-5) and blood was sampled for up to 240 min. Data were analyzed using SAAM/CONSAM. Calcium kinetics were fitted by a model with three compartments in the body and one absorption pathway from the intestine. By contrast, oxalic acid kinetics were fitted by two pools in the body and two absorption pathways from the intestine. Calcium and oxalic acid, therefore, demonstrate different absorption and distribution kinetics in rats.     

Gestational diabetes is a herald of NIDDM in Navajo women. High rate of abnormal glucose tolerance after GDM

OBJECTIVE: To estimate the rate of deterioration of glucose tolerance and evaluate risk factors for development of NIDDM in Navajo women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A retrospective analysis of 111 GDM deliveries over a 4-year period, 1983-1987, was conducted in 1994 to determine glucose tolerance status. Patients who had not developed NIDDM were recalled for a 2-h glucose tolerance test (GTT). Tested and non-tested patients were compared, as estimate of conversion to NIDDM was calculated, and risk factors for NIDDM were evaluated. A life-table analysis was developed to estimate the probability of NIDDM after GDM. RESULTS: At the time of chart review, 32 patients (29%) had already been diagnosed with NIDDM. Of the patients, 79 were offered GTT testing, and 56 (71%) returned for follow-up; 15 were diagnosed with NIDDM and 17 with impaired glucose tolerance (IGT); 47 (42%) and 64 (58%) patients in the cohort had developed NIDDM or NIDDM/IGT at the conclusion of the study period. Patients who developed NIDDM had greater BMIs, parity, and infant weights. Fasting blood glucose > 5.83 mmol/l, GTT > 41.63 mmol/l, and recurrence of GDM were associated with later NIDDM. A life-table analysis estimated a 53% likelihood of having NIDDM at an 11-year follow-up; a second model, based only on patients with known NIDDM status, predicted a 70% rate of NIDDM at an 11-year follow-up. CONCLUSIONS: A high proportion of Navajo women with GDM progressed to NIDDM. Postpartum counseling and periodic GTTs are recommended.     

Pregnant women with impaired tolerance to an oral glucose load in the afternoon: evidence suggesting that they behave metabolically as patients with gestational diabetes

OBJECTIVE: In previous studies we observed the existence of a circadian variation of the blood glucose response to oral glucose in pregnant women with higher values at 4 PM. Some women with increased risk of diabetes with normal oral glucose tolerance tests at 8 AM also had values above maximum normal levels at 4 PM. The aim of this trial was to determine the clinical significance of this impaired tolerance in the afternoon. STUDY DESIGN: Seventy-seven pregnant women with normal risk of diabetes (65 of normal weight and 12 overweight), 75 with increased risk of diabetes (26 overweight), and 12 patients with gestational diabetes were incorporated in the study. All women underwent two oral glucose tolerance tests (1.5 gm/kg) at 31 to 32 weeks' gestation at 8 AM and 4 PM with a 1-week interval. At 33 weeks' gestation a whole-day blood glucose profile was performed with usual food intake; samples were withdrawn before each meal and at 30, 60, and 120 minutes after each meal. The weight of the newborns was recorded. RESULTS: (1) Results of oral glucose tolerance tests confirmed a circadian variation of the response in all groups; (2) 37 women with increased risk of diabetes had higher values after oral glucose tolerance testing than the normal threshold at 4 PM but not at 8 AM; (3) among women with normal risk of diabetes all values were within the normal range despite the circadian variation; (4) blood glucose levels during whole-day profiles were normal in women with normal risk of diabetes and with increased risk of diabetes with normal oral glucose tolerance testing at 4 PM, whereas all women with increased risk of diabetes and impaired tolerance in the afternoon showed hyperglycemic episodes; (5) the percentage of newborns with high weight (>90th percentile) among women with increased risk of diabetes and abnormal oral glucose tolerance tests at 4 PM was similar to the percentage found in women with gestational diabetes and much higher than the one observed in women with normal oral glucose tolerance tests in the afternoon. CONCLUSIONS: The impairment of the response to oral glucose tolerance testing seen in some patients with increased risk of diabetes at 4 PM but not at 8 AM seems of clinical significance in view of the abnormal whole-day blood glucose profile these women had and the weights of the newborns.     

Metabolism of oral glucose in pancreas transplant recipients with normal and impaired glucose tolerance

To gain insight into the pathophysiology of impaired glucose tolerance in pancreas transplantation, glucose kinetics and insulin secretion were assessed after an oral glucose load in four combined pancreas-kidney recipients with impaired glucose tolerance (IPx), in five combined pancreas-kidney recipients with normal glucose tolerance, in six nondiabetic kidney transplant recipients, and in eight normal subjects employing a dual isotope technique, beta-Cell function was evaluated by calculating prehepatic insulin secretion rates, which subsequently were correlated to the ambient glucose concentrations to obtain an index of beta-cell responsiveness. Oxidative and nonoxidative glucose metabolism were assessed by indirect calorimetry. Basal insulin secretion rates, the glucose-stimulated early insulin secretion rates, as well as beta-cell responsiveness were markedly reduced in IPx than in the glucose-tolerant transplant subjects. Total systemic glucose appearance was similar in the groups with apparently comparable inhibition of systemic glucose release and increase in exogenous glucose appearance. The hyperglycemic response in IPx was due to a significant reduction in the glucose disappearance rates during the first 2 h after glucose ingestion. Nonoxidative glucose metabolism increased significantly less in IPx than in glucose-tolerant groups. Glucagon secretion was less suppressed in the early part of the study in IPx, which may have contributed to the excessive hyperglycemia. In conclusion, IPx after pancreas transplantation was characterized by 1) impaired early insulin secretion, 2) reduced beta-cell responsiveness, 3) reduced glucose uptake, 4) impaired nonoxidative glucose metabolism, and 5) impaired early inhibition of glucagon secretion.     

Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes

OBJECTIVE: To evaluate the relative value of plasma glucose (PG) at different time points in assessing glucose control of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Glycemic profiles, i.e., PG at prebreakfast (8:00 A.M.), prelunch (11:00 A.M.), postlunch (2:00 P.M.), and extended postlunch (5:00 P.M.) times over the same day, were obtained in 66 type 2 diabetic patients on an ambulatory basis. The different time points of PG were compared with a measurement of HbA1c made in a reference laboratory. RESULTS: Extended postlunch PG was lower than prebreakfast PG (104 +/- 21 vs. 133 +/- 35 mg/dl, P < 0.02) in patients demonstrating good diabetic control (HbA1c < or = 7.0%), was not different from prebreakfast PG (149 +/- 47 vs. 166 +/- 26 mg/dl, NS) in patients demonstrating fair diabetic control (7.0% < HbA1c < or = 8.5%), and was higher than prebreakfast PG (221 +/- 62 vs. 199 +/- 49 mg/dl, P < or = 0.01) in those demonstrating poor diabetic control (HbA1c < or = 8.5%). Prebreakfast, prelunch, postlunch, and extended postlunch PG values were all significantly correlated with HbA1c. Multiple linear regression analysis demonstrated that postlunch PG and extended postlunch PG correlated significantly and independently with HbA1c, but that prebreakfast PG and prelunch PG did not. Moreover, postlunch PG and extended postlunch PG demonstrated better sensitivity, specificity, and positive predictive value in predicting poor glycemic control than did prebreakfast PG or prelunch PG. CONCLUSIONS: In type 2 diabetes, postlunch PG and extended postlunch PG are better predictors of glycemic control than fasting plasma glucose (FPG). We therefore suggest that they be more widely used to supplement, or substitute for, FPG in evaluating the metabolic control of type 2 diabetic patients.     

Incidence of gestational diabetes as well as changes in insulin secretion during pregnancy. 1. Studies on pregnant women suspected of diabetes using the glucose infusion test (GIT)

Based on the glucose infusion test, we find with 17.9 per cent of a group of anamnestically tainted pregnant women gestational diabetes, and with 5.7 per cent of this group a carbohydrate tolerance with disturbed boundaries. With probands having a carbohydrate tolerance with disturbed boundaries we find a significantly more frequent IRI-high-response. This coincidence of a carbohydrate tolerance in the border range and of an IRI-high-response might correspond to the early asymptomatic stage of diabetes. In the following stages, there will take place a depression of the early insulin phase with a pathological carbohydrate tolerance of the pregnant women in the sense of a gestational diabetes. With probands exhibiting a disturbed carbohydrate tolerance, a diminished depression of free fatty acids is found. The total lipid content and cholesterol are not essentially changed. With women suffering from gestational diabetes urinary sugar excretion is significantly higher than with probands showing a normal carbohydrate tolerance.     

Lack of agreement between the World Health Organization Category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose

OBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose tolerance (IGT) status in a population with a high prevalence of diabetes. RESEARCH DESIGN AND METHODS: We analyzed the oral glucose tolerance tests (OGTTs) carried out at the Instituto Nacional de la Nutrición Salvador Zubiran (INNSZ) central laboratory from June to December 1997. We included patients with fasting plasma glucose (FPG) between 60 and 160 mg/dl. The results from the glucose tolerance test were selected as the gold standard. RESULTS: Among the 1,802 glucose tolerance test results available for analysis, 1,706 fulfilled the requirements to be included. Diabetes and IGT were remarkably more frequently diagnosed when the WHO criteria were applied. The new ADA criteria failed to diagnose 69% of WHO diabetic patients and the vast majority of WHO glucose-intolerant subjects. Using the new criteria, 82% were considered normal. Of the IFG subjects, 39% were classified as diabetic and 23% were normal according to the 2-h postchallenge glucose values. Only 37% of the IFG patients were, in fact, glucose intolerant according to the WHO criteria. CONCLUSIONS: Our results clearly show that the 1997 ADA criteria are less sensitive for diagnosing diabetes than OGTT-based WHO criteria. Even more important, there is poor agreement between the WHO category of IGT and the ADA category of IFG.     

The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS: While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol.h-1.l-1, P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol.h-1.l-1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol.h-1.l-1, P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol.h-1.l-1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol.h-1.l-1 and 7.5 +/- 0.7 nmol.h-1.l-1) was significantly greater than that on placebo (4.0 +/- 1.6 mmol.h-1.l-1 and 0.8 +/- 0.4 nmol.h-1.l-1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS: It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.