Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia

OBJECTIVE: To analyze a transcutaneous near-infrared spectroscopy system as a technique for in vivo noninvasive blood glucose monitoring during euglycemia and hypoglycemia. RESEARCH DESIGN AND METHODS: Ten nondiabetic subjects and two patients with type 1 diabetes were examined in a total of 27 studies. In each study, the subject's plasma glucose was lowered to a hypoglycemia level (approximately 55 mg/dl) followed by recovery to a glycemic level of approximately 115 mg/dl using an intravenous infusion of insulin and 20% dextrose. Plasma glucose levels were determined at 5-min intervals by standard glucose oxidase method and simultaneously by a near-infrared spectroscopic system. The plasma glucose measured by the standard method was used to create a calibration model that could predict glucose levels from the near-infrared spectral data. The two data sets were correlated during the decline and recovery in plasma glucose, within 10 mg/dl plasma glucose ranges, and were examined using the Clarke Error Grid Analysis. RESULTS: Two sets of 1,704 plasma glucose determinations were examined. The near-infrared predictions during the fall and recovery in plasma glucose were highly correlated (r = 0.96 and 0.95, respectively). When analyzed during 10 mg/dl plasma glucose segments, the mean absolute difference between the near-infrared spectroscopy method and the chemometric reference ranged from 3.3 to 4.4 mg/dl in the nondiabetic subjects and from 2.6 to 3.8 mg/dl in the patients with type 1 diabetes. Using the Error Grid Analysis, 97.7% of all the near-infrared predictions were assigned to the A-zone. CONCLUSIONS: Our findings suggest that the near-infrared spectroscopy method can accurately predict plasma glucose levels during euglycemia and hypoglycemia in humans.     

Effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes

OBJECTIVE

To assess the impact of continuous glucose monitoring on hypoglycemia in people with type 1 diabetes.

RESEARCH DESIGN AND METHODS

In this randomized, controlled, multicenter study, 120 children and adults on intensive therapy for type 1 diabetes and a screening level of glycated hemoglobin A_1c (HbA_1c) <7.5% were randomly assigned to a control group performing conventional home monitoring with a blood glucose meter and wearing a masked continuous glucose monitor every second week for five days or to a group with real-time continuous glucose monitoring. The primary outcome was the time spent in hypoglycemia (interstitial glucose concentration <63 mg/dL) over a period of 26 weeks. Analysis was by intention to treat for all randomized patients.

RESULTS

The time per day spent in hypoglycemia was significantly shorter in the continuous monitoring group than in the control group (mean ± SD 0.48 ± 0.57 and 0.97 ± 1.55 h/day, respectively; ratio of means 0.49; 95% CI 0.26–0.76; P = 0.03). HbA_1c at 26 weeks was lower in the continuous monitoring group than in the control group (difference −0.27%; 95% CI −0.47 to −0.07; P = 0.008). Time spent in 70 to 180 mg/dL normoglycemia was significantly longer in the continuous glucose monitoring group compared with the control group (mean hours per day, 17.6 vs. 16.0, P = 0.009).

CONCLUSIONS

Continuous glucose monitoring was associated with reduced time spent in hypoglycemia and a concomitant decrease in HbA_1c in children and adults with type 1 diabetes.The benefits of intensive treatment of type 1 diabetes, established almost 20 years ago (1), are difficult to achieve, despite the increased use of insulin analogs and insulin pumps, with only a minority of patients maintaining their glycated hemoglobin A_1c (HbA_1c) within the target range (2). Intensive insulin treatment and lower HbA_1c increase exposure to hypoglycemia (3,4). The risk of hypoglycemia is even higher in children and adolescents (5,6) and increases with the duration of diabetes (7). Frequent hypoglycemia is associated with hypoglycemia unawareness (8,9), which may in turn lead to reduced adherence to therapeutic decisions (10). Finally, hypoglycemia may be associated with permanent damage to the central nervous system (11) and may permanently influence cognitive functions in children (12) but not in adults (13).Recently, devices for real-time continuous glucose monitoring have been introduced to aid self-management of glycemic control and have been shown to improve HbA_1c levels in people with type 1 diabetes (14–17). In clinical practice recommendations, it has also been suggested that continuous glucose monitoring is especially useful in patients with hypoglycemia unawareness and/or frequent episodes of hypoglycemia (18). However, the hypoglycemia preventive effect of continuous glucose monitoring has not been established. Therefore, we designed a randomized, controlled, multicenter clinical trial to evaluate the effect of continuous glucose monitoring on hypoglycemia in children and adults with type 1 diabetes.     

Effect of blood glucose control on peripheral nerve function in diabetic patients

A prospective, stratified, randomized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years. The goals for conventional glucose control were the mean of fasting and 80-minute postprandial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes. The goal of rigorous glucose control was an approximation of nondiabetic glucose control. No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups. Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group, and five patients in the rigorous-control group never achieved the desired glucose control. In the remaining 20 patients, with similar baseline glucose control and peripheral nerve function characteristics, observed over a median of 2 years, improved blood glucose control (P less than 0.01) was not associated with any significant improvement in peripheral nerve function. Nevertheless, a significant (P less than 0.05) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study. If control of hyperglycemia benefits peripheral nerve function of diabetic patients, its demonstration may require a closer approximation of normoglycemia, a larger difference in glucose control between the two study groups, a longer duration of treatment, and the use of patients with more advanced peripheral nerve function abnormalities than those in this study.     

Effect of glucosamine on glucose control

OBJECTIVE: To review the literature regarding the effect of glucosamine on glucose control. DATA SOURCES: English-language articles on the effects of administration of exogenous glucosamine on glucose control were identified through a search of MEDLINE (1966-March 2006), EMBASE (1988-March 2006), and International Pharmaceutical Abstracts (1970-March 2006) databases using the search terms glucosamine, blood glucose, and diabetes mellitus. Abstracts of articles were then reviewed to determine relevance to the topic. Bibliographies of selected articles were screened for other pertinent references. DATA SYNTHESIS: Theoretically, glucosamine may alter glucose metabolism. Insulin resistance has been noted following intravenous administration of glucosamine in animal studies; however, these findings have not been confirmed in humans. Alterations in glucose control have not been documented in long-term efficacy studies using oral glucosamine for osteoarthritis or in trials of short duration conducted in healthy or diabetic subjects. The long-term effects of glucosamine in patients with diabetes have yet to be established in well-controlled trials. CONCLUSIONS: Small, short-term studies suggest that glucosamine may be used in selected patients without affecting glucose control; however, data in patients with diabetes mellitus are limited, and close monitoring for potential changes in glucose control is recommended.     

胰岛素治疗期间餐后2h血糖水平与低血糖发生的相关性研究

目的研究餐后2 h血糖(PBG2h)值与随后发生低血糖的相关性。方法对使用胰岛素治疗的糖尿病患者进行血糖监测,观察记录在PBG2h小于6 mmol/L的情况下,餐后2 h至下次进餐期间是否发生低血糖,了解低血糖的原因。结果共观察到160人231例次PBG2h小于6 mmol/L的情况,对106例次PBG2h在4.0~5.9 mmol/L进行观察,60例次出现低血糖症状或血糖≤3.9 mmol/L,46例次未出现低血糖,低血糖发生率56.6%(60/106)。PBG2h值4.0~4.4、4.5~4.9、5.0~5.4、5.5~5.9 mmol/L各段低血糖发生率分别为86.7%(13/15)、61.5%(24/39)、48.3%(14/29)、34.6%(9/26)。结论使用胰岛素的糖尿病患者当PBG2h低于6.0 mmol/L时,随后发生低血糖的风险较高。且PBG2h值越低,随后低血糖发生率越高。     

CGMS监测无知觉性低血糖的效果观察

目的 探讨CGMS监测无知觉性低血糖的效果和意义.方法 将接受胰岛素泵治疗的120例Ⅱ型糖尿病患者按照自愿的原则分为实验组和对照组,实验组使用CGMS,对照组使用强生血糖仪监测血糖,比较2组对患者发生无知觉性低血糖的检测效果和住院期间控制血糖需支付的医疗费用.结果 实验组对Ⅱ型糖尿病治疗中无知觉性低血糖检测率明显高于对照组(P＜0.01);实验组患者住院期间控制血糖的平均费用与对照组无明显差异(P＞0.05).结论 CGMS能准确有效地监测无知觉性低血糖,及时调整胰岛素用量,减少低血糖发生率,从而降低住院期间控制血糖需支付的总费用.     

Evidence for elevated glucose threshold in patients with impaired glucose tolerance and symptoms of hypoglycemia during OGTT

We evaluated the relationship between hypoglycemic symptoms, glucose nadir levels, and hormone changes in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT). The peak counterregulatory hormone response was determined at the glucose nadir identified by continuous glucose monitoring. Eight patients with IGT who had symptoms and signs typical of hypoglycemia at the glucose nadir were compared with completely asymptomatic subjects (5 IGT patients and 13 patients who had normal glucose tolerance [NGT]). The mean glucose nadir of symptomatic IGT patients was 3.50 +/- 0.46 mM, which was not statistically different from the mean of asymptomatic NGT patients (4.10 +/- 0.56 mM) but was significantly lower than that for asymptomatic IGT patients (5.10 +/- 0.81 mM, P less than 0.001). Seven of 8 symptomatic IGT patients had glucose levels that never fell below the range of glucose nadirs for asymptomatic NGT patients. However, the symptomatic IGT group had significantly higher levels of growth hormone, cortisol, epinephrine, and norepinephrine than the asymptomatic groups in response to the nadir. We conclude that patients with IGT are capable of experiencing signs and symptoms of hypoglycemia at physiological glucose levels during OGTT with reflex stimulation of counterregulatory hormone release. This may indicate that symptomatic IGT patients have a higher glucose threshold for eliciting characteristic hypoglycemic symptom episodes than individuals with NGT.     

CGMS监测无知觉性低血糖的效果观察

目的 探讨CGMS监测无知觉性低血糖的效果和意义.方法 将接受胰岛素泵治疗的120例Ⅱ型糖尿病患者按照自愿的原则分为实验组和对照组,实验组使用CGMS,对照组使用强生血糖仪监测血糖,比较2组对患者发生无知觉性低血糖的检测效果和住院期间控制血糖需支付的医疗费用.结果 实验组对Ⅱ型糖尿病治疗中无知觉性低血糖检测率明显高于对照组(P＜0.01);实验组患者住院期间控制血糖的平均费用与对照组无明显差异(P＞0.05).结论 CGMS能准确有效地监测无知觉性低血糖,及时调整胰岛素用量,减少低血糖发生率,从而降低住院期间控制血糖需支付的总费用.     

Effect of sucrose-containing snacks on blood glucose control

To determine whether ingestion of sucrose-containing snacks would affect blood glucose (BG) control, 16 subjects with insulin-dependent diabetes mellitus participated in a 5-day double-blind study at a diabetes camp. Eight subjects in the sucrose group ate sucrose-sweetened snacks twice a day, and 8 subjects in the control group ingested snacks that were sweetened with aspartame. The percentage of total daily calories derived from added sucrose was 7% for the sucrose group and 1% for the control group. Metabolic control was assessed by daily capillary BG measurements obtained before meals and the bedtime snack and by determination of serum fructosamine (F) concentrations on arrival at camp (day 0) and after 5 days on the study protocol (day 5). No significant difference was seen between the groups on day 0 (sucrose group [mean +/- SD]: BG 9.9 +/- 3.6 mM, F 3.54 +/- 0.38 mM; control group: BG 9.1 +/- 2.8 mM, F 3.74 +/- 0.71 mM) or day 5 (sucrose group: BG 8.8 +/- 2.6 mM, F 2.94 +/- 0.32 mM; control group: BG 7.4 +/- 2.8 mM, F 2.92 +/- 0.59 mM). We conclude that ingestion of sucrose, added to snacks in an amount up to 7% of total energy intake, does not adversely affect short-term BG control.     

Effect of propranolol on delayed glucose recovery after insulin-induced hypoglycemia in normal and diabetic subjects

In order to evaluate the influence of beta-adrenergic blockade on recovery from insulin-induced hypoglycemia, we compared the effect of saline or propranolol infusion during concomitant hypoglycemia in normal and type I diabetic persons. The diabetic subjects were initially rendered euglycemic with a basal insulin infusion. Glucose turnover was measured using [3-3H]glucose tracer. Propranolol caused a small but significant delay in glucose recovery in normal subjects, with plasma glucose only 80% of the values seen during saline infusion 1 h after hypoglycemia (P less than 0.005). This delay was caused by a 70% reduction in the rebound glucose output, which was responsible for posthypoglycemic recovery. In the diabetic subjects, glucose recovery was significantly delayed as compared with that in normal persons, even in the absence of propranolol, and associated with reduced secretion of epinephrine and glucagon. Moreover, the addition of propranolol caused a further 50% reduction in glucose recovery such that plasma glucose remained below 50 mg/dl for 3 h. In contrast to normals, propranolol did not inhibit the already blunted rebound in glucose output. However, propranolol prevented the decline in glucose utilization that occurred when saline alone was infused. During saline infusion, glucose uptake was at basal rates by 60 min whereas, during propranolol administration, glucose uptake remained above baseline until 180 min (P less than 0.01). Thus, propranolol may interfere with glucose recovery after insulin-induced hypoglycemia in diabetic patients by blocking epinephrine's inhibition of glucose utilization whereas, in normals, propranolol's effect is largely accounted for by blockade of epinephrine-induced hepatic glucose production.     

血糖控制水平对高血压糖尿病合并脑出血患者并发症的影响

目的探讨血糖控制水平对高血压糖尿病(diabetes mellitus,DM)合并脑出血患者并发症发生的影响。方法将156例脑出血患者按血糖控制水平分为DM血糖控制良好组(95例)和DM血糖控制不良组(61例),比较两组患者死亡率和并发症的发生情况。结果 DM血糖控制不良组患者肺部感染、压疮的发生率及死亡率高于DM血糖控制良好组,两组比较,差异具有统计学意义(均P<0.05)。结论血糖控制不良会增加高血压糖尿病合并脑出血患者死亡率及肺部感染和压疮的发生率。加强血糖的监测与控制,做好患者和家属的健康指导,对降低并发症的发生具有重要意义。     

Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats.

The ventromedial hypothalamic nucleus (VMH) is necessary for the integrated hormonal response to hypoglycemia. To determine the role of the VMH as a glucose sensor, we performed experiments designed to specifically prevent glucopenia in the VMH, while producing hypoglycemia elsewhere. We used awake chronically catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D-glucose) was combined with a sequential euglycemic-hypoglycemic clamp. In two control groups the VMH was perfused either with (a) an iso-osmotic solution lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic hypoglycemia glucagon and catecholamine concentrations promptly increased in the control animals perfused with either 100 mM L-glucose or the iso-osmotic solution lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release was inhibited in the animals in which the VMH was perfused with D-glucose; hormonal secretion was partially suppressed by the VMH perfusion with 15 mM D-glucose and suppressed by approximately 85% when the VMH was perfused with 100 mM D-glucose, as compared with the control groups. We conclude that the VMH must sense hypoglycemia for full activation of catecholamine and glucagon secretion and that it is a key glucose sensor for hypoglycemic counterregulation.     

Effect of seat surface inclination on postural control during reaching in preterm children with cerebral palsy

BACKGROUND AND PURPOSE: Because it is debatable whether seat surface inclination improves motor function in children with cerebral palsy (CP), the effect of seat surface tilting on postural control and quality of reaching was studied. SUBJECTS: The subjects were 58 children with CP aged 2 to 11 years (34 with unilateral spastic CP, 24 with bilateral spastic CP). METHODS: During the task of reaching movements, surface electromyographic and kinematic data were recorded for posture and reaching with the dominant arm in 3 sitting conditions: horizontal seat surface, seat surface tilted forward 15 degrees, and seat surface tilted backward 15 degrees. RESULTS: In the children with unilateral spastic CP, forward tilting improved postural efficiency and quality of reaching. In the children with bilateral spastic CP, both forward and backward tilting of the seat surface was associated with more postural instability and did not affect the quality of reaching. DISCUSSION AND CONCLUSION: The results suggest that, in terms of postural control and quality of reaching, children with unilateral spastic CP benefit from a forward-tilted position and children with bilateral spastic CP benefit from a horizontal sitting position.     

Role of cortisol in the pathogenesis of deficient counterregulation after antecedent hypoglycemia in normal humans.

The aim of this study was to determine the role of increased plasma cortisol levels in the pathogenesis of hypoglycemia-associated autonomic failure. Experiments were carried out on 16 lean, healthy, overnight fasted male subjects. One group (n = 8) underwent two separate, 2-d randomized experiments separated by at least 2 mo. On day 1 insulin was infused at a rate of 1.5 mU/kg per min and 2 h clamped hypoglycemia (53 +/- 2 mg/dl) or euglycemia (93 +/- 3 mg/dl) was obtained during morning and afternoon. The next morning subjects underwent a 2-h hyperinsulinemic (1.5 mU/kg per min) hypoglycemic (53 +/- 2 mg/dl) clamp study. In the other group (n = 8), day 1 consisted of morning and afternoon 2-h clamped hyperinsulinemic euglycemia with cortisol infused to stimulate levels of plasma cortisol occurring during clamped hypoglycemia (53 mg/dl). The next morning (day 2) subjects underwent a 2-h hyperinsulinemic hypoglycemic clamp identical to the first group. Despite equivalent day 2 plasma glucose and insulin levels, steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, ACTH and muscle sympathetic nerve activity (MSNA) values were significantly (R < 0.01) blunted after day 1 cortisol infusion compared to antecedent euglycemia. Compared to day 1 cortisol, antecedent hypoglycemia produced similar blunted day 2 responses of epinephrine, norepinephrine, pancreatic polypeptide and MSNA compared to day 1 cortisol. Antecedent hypoglycemia, however, produced a more pronounced blunting of plasma glucagon, ACTH, and hepatic glucose production compared to day 1 cortisol. We conclude that in healthy overnight fasted men (a) antecedent physiologic increases of plasma cortisol can significantly blunt epinephrine, norepinephrine, glucagon, and MSNA responses to subsequent hypoglycemia and (b) these data suggest that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure.