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Evaluation of a new real-time blood continuous glucose monitoring system in pregnant women without gestational diabetes. A pilot study.

The incidence of gestational diabetes mellitus (GDM) has reached epidemic proportions in the United States, affecting 200,000 pregnant women annually. Controversies exist regarding whether the glucose levels used to diagnose GDM in pregnancy should be lowered since similar fetal complications are seen in women with GDM as well as in nondiabetic women. Although GDM has been extensively studied, the effects of the earlier stage of glucose intolerance are not well understood. The objectives of this descriptive, comparative, correlational pilot study include assessment of real-time blood glucose concentrations in women (20) with idiopathic macrosomia and/or polyhydramnios but with a normal baseline glucose screening test. This group was compared to pregnant women (20) without idiopathic macrosomia and/or polyhydromnios as confirmed by normal ultrasounds (controls). All subjects had a normal screeing test and/or a 3-hour Glucose Tolerance Test earlier in the pregnancy and wore a continuous glucose monitoring system for 72 hours. No adverse maternal complications were seen. Neonatal complications included macrosomia, shoulder dystocia, and hyperbilirubinemia. There was no significant association between real-time blood glucose levels and adverse maternal or fetal/neonatal complications. There is little evidence available regarding real-time physiologic glycemic levels in pregnant women. The findings of our pilot study provide baseline data for the design of a larger study to compare blood glucose levels and complications in euglycemic women and compare to women with those impaired glucose tolerance.

Adult↗

Hepatic insulin resistance after pancreas transplantation in type I diabetes.

Hyperinsulinemia and peripheral insulin resistance caused by systemic insulin delivery and prednisone therapy are recognized consequences of pancreas transplantation. However, there is little information about insulin action on the liver. To investigate hepatic insulin sensitivity in recipients of pancreas transplants, we devised a staged euglycemic hyperinsulinemic clamp to measure hepatic glucose production (HGP) in 10 type I diabetic pancreas transplant recipients, 10 pair-matched healthy control subjects, and 6 nondiabetic kidney transplant recipients. Clamps were performed in two sequential stages. In stage 1, a 2-h low-dose insulin infusion (0.4 mU.kg-1.min-1) was used to partially suppress HGP. In stage 2, insulin-mediated suppression of HGP was challenged by a 1.5-h glucagon infusion (0.8 ng.kg-1.min-1), while continuing the hyperinsulinemic euglycemic-clamp conditions. During both stages, somatostatin (250 micrograms/h) was infused to suppress endogenous insulin secretion. All subjects underwent stage 1, and all except one pancreas recipient and a respective matched healthy control subject completed stage 2. Fasting HGP was greater in pancreas recipients than in healthy control subjects (15.1 +/- 0.7 vs. 12.0 +/- 0.4 mumol.l-1.kg-1.min-1, P < 0.005) but similar in healthy control subjects and in kidney recipients. During stage 2, both total (706 +/- 28 vs. 469 +/- 31 mumol.l-1.kg-1, P < 0.005) and incremental (62 +/- 20 vs. -21 +/- 16 mumol.l-1.kg-1, P < 0.005) HGP responses to glucagon infusion were significantly greater in pancreas recipients than in healthy control subjects. Changes in HGP in kidney recipients during stage 2 were not significantly different from those in healthy control subjects. In conclusion, fasting HGP is increased in pancreas transplant recipients. Furthermore, recipients have hepatic insulin resistance as demonstrated by an enhanced stimulatory effect of glucagon on HGP during insulin-mediated HGP suppression. Because the magnitude of hepatic insulin resistance was a significant (P < 0.01) predictor of HbA1c level, we suggest that variable hepatic insulin resistance may be responsible for some of the variance observed in glycemic levels after successful pancreas transplantation.

Adult↗

Public health and clinical implications of high hemoglobin A1c levels and weight in younger adult Native American people with diabetes.

BACKGROUND: Type 2 diabetes mellitus is a major public health issue for Native American people. Because glycemic levels are predictive of diabetes outcome, understanding determinants of high hemoglobin A(1c) (HbA(1c)) levels may provide targets for prevention efforts. OBJECTIVES: To investigate determinants of high HbA(1c) levels in Native American people. METHODS: We conducted a population-based, cross-sectional study of 206 participants with diabetes from 8 Native American communities in New Mexico. We used linear regression to assess the relationship of HbA(1c) level with age, body mass index (BMI), treatment type, duration of diabetes, physical activity, and diet. RESULTS: Age, dietary pattern, and treatment type were determinants of HbA(1c) levels. Participants younger than 55 years had the highest adjusted HbA(1c) levels at 9.5% and those 65 years and older had the lowest levels at 7.8%. According to a participant's dietary intake, HbA(1c) levels were highest for those who consumed the most fat and sugar, and high consumption of fat and sugar affected HbA(1c) levels most among those younger than 55 years. Participants treated with insulin had the highest hemoglobin A(1c) levels. Physical activity was not associated with HbA(1c) level. CONCLUSIONS: We found an increasing severity of diabetes among younger people. To avoid increased morbidity and mortality in the future, young Native American adults with diabetes need vigorous therapy to maintain tight glucose control. Arch Intern Med. 2000;160:3471-3476.

Adolescent↗

Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient.

We report a case of long-term (>4 yr) successful intrahepatic islet transplantation into a type 1 diabetic patient chronically immunosuppressed for a prior kidney graft. The exogenous insulin requirement decreased progressively after transplantation, and insulin treatment was withdrawn at 6 months. Glycosylated hemoglobin levels were in the normal range at 1 and 2 yr (5.3%) and increased slightly above the upper normal limit at 3 and 4 yr (6.3% and 6.4%). Fasting C peptide levels remained stable during the entire follow-up, but the proinsulin to insulin ratios increased dramatically at yr 3. Glycemic levels after an oral glucose tolerance test showed a diabetic profile at 1 yr, a normal profile at 2 yr, and an impaired glucose tolerance profile at 3 yr. Intravenous glucose tolerance test-induced first phase insulin release, present at 1 and 2 yr, disappeared at 3 yr. Diabetes-related autoantibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, and tyrosine phosphatase-like protein antibodies) were undetectable before transplantation and remained so during the entire follow-up. The patient died of myocardial infarction 50 months after transplantation while she was still in good metabolic control (glycosylated hemoglobin, <6.8%) in the absence of exogenous insulin administration. The autoptic liver showed well granulated islets, richly vascularized and without evidence of lympho-mononuclear cell infiltration. The morphometrically extrapolated intrahepatic beta-cell mass was 99.9 mg. In conclusion, this successful islet graft showed a bell-shaped clinical effect, maximal at 2 yr after transplantation, followed by a slow progressive decline. The absence of allo- and autoreactivities against the transplanted islets points to a nonimmune-mediated beta-cell loss as the cause of graft functional deterioration.

Adult↗

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

Acute Disease↗

Reversed circadian blood pressure rhythm independently predicts endstage renal failure in non-insulin-dependent diabetes mellitus subjects.

To investigate the significance of reversed circadian blood pressure (BP) rhythm as a predictor for diabetic endstage renal failure, introduction of hemodialysis (HD) was determined as an end point in 325 noninsulin-dependent diabetes mellitus (NIDDM) subjects, in whom 24-h BPs had been monitored during their first admissions between 1988 and 1996. Circadian BP rhythm was analyzed by the COSINOR method, as previously reported. After exclusion of 68 dropout subjects, 257 were recruited for further analyses, in which 194 had normal circadian BP rhythms (N), and the remaining 63 had reversed rhythms (R). During this follow-up period, the numbers of HD-introduced subjects in N and R were 6 and 16, respectively, showing a higher prevalence in the latter (p < 0.001, chi2 test). Follow-up periods were significantly shorter in HD-introduced diabetic subjects of N and R than those in HD-free subjects of each group. In baseline characteristics, there were no differences in age, gender, or serum creatinine between HD-free and HD-introduced subjects of N or R. With regard to microvascular complications, the degree of retinopathy and nephropathy in N and R tended to be more pronounced in HD-introduced subjects than in HD-free subjects. Further, mean levels of circadian mean BP rhythms in HD-introduced subjects of N or R were similarly high, compared with those in HD-free subjects of each group, irrespective of circadian BP pattern. Unadjusted HD-free times were estimated by the Kaplan-Meier method, with a significant difference noted between N and R (p < 0.001; log-rank test). The Cox proportional-hazards model adjusted for circadian BP pattern, age, gender, blood pressure level, glycemic control, duration of diabetes, serum total protein, and serum creatinine demonstrated that circadian BP pattern, age, gender (female), blood pressure level (hypertension), and serum creatinine exhibited significant high relative risks. Thus, our data suggest that reversed circadian BP rhythm is an independent predictor of endstage renal failure in NIDDM subjects.

Adult↗

Blood glucose monitoring technology: translating data into practice.

OBJECTIVE: To describe how blood glucose software downloading has been successfully incorporated into a clinical practice by focusing on key data--frequency of testing, blood glucose averages, and standard deviations. METHODS: The development of self-monitoring of blood glucose, including the spectrum of blood glucose monitors and diabetes management software programs, is reviewed, and clinical applications in specific cases are presented. RESULTS: Since the 1980s, motivated patients with diabetes have used portable meters to monitor their blood glucose levels. The practice became a standard of care in 1993, when the Diabetes Control and Complications Trial demonstrated that maintaining near-normal glycemic levels could prevent or delay the long-term complications of type 1 diabetes. Since then, the technology of blood glucose monitoring has burgeoned--an array of memory meters and downloading software offers clinicians and patients more information than ever before. Yet, because health-care providers and patients are often at a loss to interpret and apply the resulting plethora of data, few take full advantage of the latest technology. Important insights are shared about certain downloaded information from glucose meters that will help improve or maintain glycemic control. CONCLUSION: Data downloaded from glucose meters can be used in conjunction with written records in logbooks to evaluate glucose patterns and formulate more precise and efficacious therapeutic regimens.

Adolescent↗

Cerebral blood flow and plasma volume during hyperglycemia in the conscious rat.

Cerebral blood flow (CBF) and cerebral plasma volume (CPV) were measured under steady-state hyperglycemic conditions in the hemispheres and brainstem-cerebellum of conscious rats. There groups of hyperglycemic animals each having a different level of plasma glucose concentration, 25, 33.3, 44.4 mmol/l, and a normoglycemic control group were studied. CBF was not affected at the hyperglycemic levels of 25 and 33.3 mmol/l. Mean hemispheric and brainstem-cerebellum CBF values appeared lower than in controls at the highest glycemic level although the differences were not statistically significant. CPV was found to be unchanged at the hyperglycemic level of 25 mmol/l, while it was found to be increased in the hemispheres of the animals whose plasma glucose concentration had been elevated to 33.3 and 44.4 mmol/l. The results of the study do not support the claim that hyperglycemia may enhance ischemic brain injury by reducing CBF.

Animals↗

Fetal biophysical activities in third-trimester pregnancies complicated by diabetes mellitus.

OBJECTIVE: Our purpose was to compare third-trimester fetal biophysical activities in normal and well-controlled insulin-dependent diabetic pregnancies. STUDY DESIGN: We performed serial bimonthly fetal biophysical studies from 30 to 38 weeks in 18 normal and 18 well-controlled insulin-dependent diabetic pregnancies (White classes B through D). Each study contained 60 minutes of simultaneous ultrasonographic recordings of fetal breathing movements and rates, baseline heart rate, and body movements. Mean daily blood glucose levels of diabetic patients were determined from home monitors; HbA1c was determined every 6 weeks and ultrasonographic fetal growth rates every 3 weeks. Data were compared with t tests, analysis of variance with repeated measures, and chi 2 tests. RESULTS: Women in the diabetic group maintained good glycemic control and were delivered of normal infants of weights similar to those of nondiabetic gravidas. Their fetuses had higher mean incidences of fetal breathing movement, fetal heart rates, and fetal breathing rates but lower fetal movements and fetal heart rate acceleration counts than did controls throughout the study. Neither short- nor long-term maternal glycemic levels correlated well with fetal biophysical performance. CONCLUSIONS: In spite of good maternal glycemic control fetuses of diabetic women behaved differently from those of nondiabetic women. Modulation of their biophysical activities may be affected by maternal glycemic status before the last trimester. Different standards might need to be applied to interpret their tests.

Adult↗

Ingestive behaviors and metabolic fuels after central injections of 5-HT1A and 5-HT1D/1B receptors agonists in the pigeon.

The effects of intracerebroventricular injections of 8-OH-DPAT (a 5-HT1A agonist; 3, 15 or 30 nmol) or GR46611 (a 5-HT1B/1D agonist; 3, 15 or 30 nmol) on feeding, drinking, preening and sleep-like behaviors were investigated in free-feeding (FF) pigeons. The effects of these 5-HT agonists on blood glucose and free fatty acids levels were also examined. Injections of 8-OH-DPAT evoked intense lipolytic and dipsogenic effects, but failed to affect feeding, non-ingestive behaviors and glycemic levels. On the other hand, GR46611 evoked significant increases in food intake (at the higher dose), as well as lipolytic and hyperglycemic effects, but left drinking and other non-ingestive behaviors unchanged. These effects are opposed to those found in rodents, and may be associated with the diverse, species-specific nature and distribution of these receptors, underscoring the need to examine the functional aspects of the 5-HT1 receptor family in a more extensive range of non-rodent species.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Catecholaminergic projections from the solitary tract nucleus to the perifornical hypothalamus.

The source of adrenergic and other catecholaminergic fibers innervating the perifornical lateral hypothalamus was localized in the medulla after combination of Fluoro-Gold retrograde tracing and immunohistochemistry for either tyrosine-hydroxylase or phenylethanolamine-N-methyltransferase. Following perifornical injections, Fluoro-Gold-labeled neurons were observed mainly in regions including the noradrenergic and adrenergic cell groups. In the caudal solitary tract nucleus, two kinds of doubly labeled neurons were found: a) numerous noradrenergic neurons in the A2 group at the level of, or caudal to the area postrema; b) some adrenergic neurons in the C2 group at a level immediately rostral to the area postrema. These catecholaminergic neurons connecting the caudal solitary tract nucleus to the perifornical hypothalamus might convey feeding relevant information such as glycemic level or satiety signals.

Animals↗

Partial preservation of pancreatic beta-cells by vanadium: evidence for long-term amelioration of diabetes.

Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained for 3 days (DT3) or 14 days (DT14) post-STZ, after which vanadium was withdrawn. At 4 to 5 weeks post-STZ and following long-term withdrawal from vanadium, DT14 rats demonstrated levels of food and fluid intake and glucose tolerance that were not significantly different from those of age-matched untreated nondiabetic rats, and had significantly reduced glycemic levels in the fed state compared with D and DT3 groups. The proportion of animals that were euglycemic (fed plasma glucose < 9.0 mmol/L) was significant in DT14 (five of 10) relative to D (one of 10) and DT3 (one of 10) (P = .01). All euglycemic animals had an improved pancreatic insulin content that, albeit low (12% of control), was strongly linked to euglycemia in the fed state (r = -.91, P < .0001). Moreover, the highly significant correlation persisted with the analysis of untreated STZ-rats alone (r = -.95, P < .0001). Similarly, improvements in glucose tolerance and insulin secretory function in euglycemic rats were strongly correlated with small changes in residual insulin content. Hence, as vanadium pretreatment did not prevent STZ-induced beta-cytotoxicity, the vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of pancreatic beta cells that initially survived STZ toxicity. The partial preservation of pancreatic beta cells, albeit small in proportion to the total insulin store, was both critical and sufficient for a long-term reversal of the diabetic state. These results suggest that apparently modest effects in preserving residual pancreatic insulin content can have profound consequences on glucose homeostasis and may bear important implications for interventions that have "limited" protective effects on beta cells.

Animals↗

Health and economic impact of combining metformin with nateglinide to achieve glycemic control: Comparison of the lifetime costs of complications in the U.K.

BACKGROUND: To reduce the likelihood of complications in persons with type 2 diabetes, it is critical to control hyperglycaemia. Monotherapy with metformin or insulin secretagogues may fail to sustain control after an initial reduction in glycemic levels. Thus, combining metformin with other agents is frequently necessary. These analyses model the potential long-term economic and health impact of using combination therapy to improve glycemic control. METHODS: An existing model that simulates the long-term course of type 2 diabetes in relation to glycosylated haemoglobin (HbA1c) and post-prandial glucose (PPG) was used to compare the combination of nateglinide with metformin to monotherapy with metformin. Complication rates were estimated for major diabetes-related complications (macrovascular and microvascular) based on existing epidemiologic studies and clinical trial data. Utilities and costs were estimated using data collected in the United Kingdom Prospective Diabetes Study (UKPDS). Survival, life years gained (LYG), quality-adjusted life years (QALY), complication rates and associated costs were estimated. Costs were discounted at 6% and benefits at 1.5% per year. RESULTS: Combination therapy was predicted to reduce complication rates and associated costs compared with metformin. Survival increased by 0.39 (0.32 discounted) and QALY by 0.46 years (0.37 discounted) implying costs of pound 6,772 per discounted LYG and pound 5,609 per discounted QALY. Sensitivity analyses showed the results to be consistent over broad ranges. CONCLUSION: Although drug treatment costs are increased by combination therapy, this cost is expected to be partially offset by a reduction in the costs of treating long-term diabetes complications.

Journal Article↗

Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant.

CONTEXT: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. OBJECTIVES: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. DESIGN: This was a multicenter, open-label, 32-wk trial study. SETTING: The study was performed at outpatient clinics. PATIENTS: Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. INTERVENTION: Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. MAIN OUTCOME MEASURES: The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion. RESULTS: At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P < or = 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. CONCLUSIONS: Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.

Acromegaly↗

Training to estimate blood glucose and to form associations with initial hunger.

BACKGROUND: The will to eat is a decision associated with conditioned responses and with unconditioned body sensations that reflect changes in metabolic biomarkers. Here, we investigate whether this decision can be delayed until blood glucose is allowed to fall to low levels, when presumably feeding behavior is mostly unconditioned. Following such an eating pattern might avoid some of the metabolic risk factors that are associated with high glycemia. RESULTS: In this 7-week study, patients were trained to estimate their blood glucose at meal times by associating feelings of hunger with glycemic levels determined by standard blood glucose monitors and to eat only when glycemia was < 85 mg/dL. At the end of the 7-week training period, estimated and measured glycemic values were found to be linearly correlated in the trained group (r = 0.82; p = 0.0001) but not in the control (untrained) group (r = 0.10; p = 0.40). Fewer subjects in the trained group were hungry than those in the control group (p = 0.001). The 18 hungry subjects of the trained group had significantly lower glucose levels (80.1 +/- 6.3 mg/dL) than the 42 hungry control subjects (89.2 +/- 10.2 mg/dL; p = 0.01). Moreover, the trained hungry subjects estimated their glycemia (78.1 +/- 6.7 mg/dL; estimation error: 3.2 +/- 2.4% of the measured glycemia) more accurately than the control hungry subjects (75.9 +/- 9.8 mg/dL; estimation error: 16.7 +/- 11.0%; p = 0.0001). Also the estimation error of the entire trained group (4.7 +/- 3.6%) was significantly lower than that of the control group (17.1 +/- 11.5%; p = 0.0001). A value of glycemia at initial feelings of hunger was provisionally identified as 87 mg/dL. Below this level, estimation showed lower error in both trained (p = 0.04) and control subjects (p = 0.001). CONCLUSION: Subjects could be trained to accurately estimate their blood glucose and to recognize their sensations of initial hunger at low glucose concentrations. These results suggest that it is possible to make a behavioral distinction between unconditioned and conditioned hunger, and to achieve a cognitive will to eat by training.

Journal Article↗

Sensitivity of nucleus tractus solitarius neurons to induced moderate hyperglycemia, with special reference to catecholaminergic regions.

Extracellular single-unit recordings have been carried out in the caudal part of the nucleus tractus solitarius of male rats anesthetized by i.v. infusion with Ketamine. The sensitivity of 38 cells to 0.2 ml of 0.55 M glucose i.v. administration has been studied. The spike frequency of 75% of these cells was affected by the induced moderate hyperglycemia and a majority of them was activated. Immunohistochemical data on 9 glycemia-sensitive neurons showed that all recording sites were within TH-immunoreactive regions of the caudal part of the nucleus (either in the A2 noradrenergic group, or the C2 adrenergic group). These results confirm the existence of glycemia-sensitive neurons in the nucleus tractus solitarius, and suggest that these cells might mediate the effects of physiological fluctuations in blood glucose level on the control of food intake and metabolic regulations. The localization of these cells in catecholaminergic regions suggests that adrenaline and/or noradrenaline efferents might convey feeding relevant information concerning glycemic level or satiety signal from the nucleus tractus solitarius to forebrain structures involved in food intake, such as the perifornical lateral hypothalamic area and the paraventricular nucleus.

Animals↗

Four-year follow-up of glucose tolerance and beta-cell function in nondiabetic cystic fibrosis patients.

Plasma glucose and insulin responses to oral glucose load were investigated and reinvestigated approximately 4 years later in 29 cystic fibrosis children and adolescents with initially normal fasting blood glucose levels. Patients' clinical status was evaluated at the time of both oral glucose tolerance tests. With respect to the basal test, the second one elicited blunted insulin responses and enhanced glycemic levels. Moreover, the prevalence of patients with diabetic glucose tolerance was significantly increased at the second evaluation and insulin secretion was markedly reduced in these patients. Deterioration of glucose tolerance and/or of insulin secretion over time was never accompanied by a significant worsening of clinical and/or nutritional status. In conclusion, in cystic fibrosis subjects with fasting euglycemia (a) both insulin secretion and glucose tolerance deteriorate during a 4-year follow-up, (b) an insulin secretion decrease is more evident in patients who develop diabetic glucose tolerance and (c) these metabolic changes are not significantly linked to a worsening of either nutritional or clinical parameters, even in the patients who develop diabetic glucose tolerance.

Adolescent↗

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.

Adult↗