早期胰岛素强化序贯治疗在ICU中的临床应用

本文通过复习相关文献资料，就早期胰岛素强化序贯治疗在ICU病人治疗中应用的几个主要方面进行扼要的综述，以利临床医生的参考。     

Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU·m^–2min^–1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r=0.65, p<0.02 and 0.0 mmol/l glucose 6-phosphate: r= 0.91, p<0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.     

A method for assessing quality of control from glucose profiles.

AIM: As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. METHODS: We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). RESULTS: The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). CONCLUSIONS: The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability.     

Is the effect of acute hyperglycaemia on interdigestive antroduodenal motility and small-bowel transit mediated by insulin?

Acute hyperglycaemia inhibits antroduodenal motility. In non-diabetic subjects this inhibitory effect may result from reactive endogenous hyperinsulinaemia. Therefore, we investigated the effects of hyperinsulinaemia during both hyperglycaemia and euglycaemia on interdigestive antroduodenal motility (perfusion manometry) and duodenocaecal transit time (DCTT; lactulose breath-H₂ test). Six healthy volunteers (age 20–26 years) were studied for 240 min on three separate occasions in random order during: (a) i.v. saline (control); (b) acute hyperglycaemic hyperinsulinaemia (HG) with plasma glucose at 15 mmol L^?1; and (c) euglycaemic hyperinsulinaemia (HI) with plasma insulin at 80 mU L^?1 and glucose at 4–5 mmol L^?1. Results: DCTT was significantly (P < 0.05) prolonged during HG (158 ± 23 min) compared with control (95 ± 25 min), whereas HI had no effect (100 ± 17 min). Mean duration of complete migrating motor complex (MMC) cycles was significantly (P < 0.05) reduced during HG (63 ± 9 min) compared with control (103 ± 15 min) and HI (105 ± 16 min), which resulted from a significantly (P < 0.05) shorter duration of phase II. Antral motility was significantly (P < 0.05) reduced during both HI (20 ± 8 contractions 240 min^?1) and HG (9 ± 5) compared with control (43 ± 7). It is concluded that in healthy subjects hyperglycaemia prolongs DCTT, increases duodenal MMC cycle frequency and inhibits antral motility. Hyperinsulinaemia reduces antral motor activity but has no effect on interdigestive duodenal motility or DCTT. Thus, other factors, apart from insulin, mediate the inhibitory effect of hyperglycaemia on interdigestive intestinal motility and transit.     

A nocturnal nasogastric feeding programme in cystic fibrosis adults

Fourteen adult patients (mean age 22.5 years, range 18–35) with cystic fibrosis undertook nocturnal nasogastric feeding for a mean period of 14.7 (range 6–18) months consuming an average of 1042 ml of a high energy feed on five nights of each week. Following this protocol all patients gained weight (mean weight gain 5.4 kg, range 2–17). For the group as a whole, lung function remained stable during the period of feeding; however a significant correlation between improvement in lung function and weight gain was demonstrated. Hyperglycaemia during feeding in this adult population was common (9/14, 64%) but was easily controlled with insulin therapy.     

The prevalence of retinopathy in subjects with and without type 2 diabetes mellitus

Purpose:  To evaluate the prevalence of and risk factors for, retinopathy in a geographically defined population with type 2 diabetes mellitus compared with a control group of subjects without diabetes, matched by age, sex and residence in order to find the retinopathy attributable to type 2 diabetes. Methods:  The study populations are, on one hand, a prevalence cohort of subjects with type 2 diabetes resident in the community of Laxå, Sweden, and on the other a control group, matched by age, gender and residence with those with a diagnosis of type 2 diabetes mellitus. Retinopathy was graded from fundus photographs using a modification of the Early Treatment Retinopathy Study (ETDRS) adaptation of the modified Airlie House classification of diabetic retinopathy (DR). Results:  Any retinopathy was found in 34.6% in the type 2 diabetes cohort and in 8.8% in the control group without diabetes. Among the diabetic patients, any retinopathy was significantly associated with duration of diabetes (p = 0.0001), HbA1c (p = 0.0056), systolic blood pressure (p = 0.0091) and lower serum cholesterol (p = 0.0197) in multivariate logistic regression analyses. Having retinopathy in the control group was associated only with systolic blood pressure (p = 0.0014) in logistic regression analysis. Conclusions:  The prevalence of retinopathy among patients with type 2 diabetes in Laxå, Sweden, was similar or somewhat lower compared with other studies in the Nordic countries. The prevalence of retinopathy in a control group without diabetes equalled numbers from population studies worldwide. Our study indicates that the retinopathy that can be attributed to hyperglycaemia in the diabetic state is less common than is usually accounted for. A considerable fraction of retinopathy in subjects with diabetes may instead be due to other factors such as hypertension and should thus be treated correspondingly.     

Plasma oxidized high-density lipoprotein and glycated apolipoprotein A-I concentrations in ST-segment elevation myocardial infarction patients with stress hyperglycaemia or high thrombus burden

Abstract

Background: High-density lipoprotein (HDL) particles exert many beneficial actions that may help protect against cardiovascular disease. However, recent work has demonstrated that HDL can be oxidized and glycated under certain circumstances and may become pro-atherogenic. The present study investigated the impact of oxidized high-density lipoprotein (ox-HDL) and glycated apolipoprotein A-I (gly-ApoA-I) in patients presenting with ST-elevation myocardial infarction (STEMI).

Methods: We assessed 55 consecutive patients with STEMI. Patients were divided into: (1) a stress hyperglycaemia (SH) and a no SH group; and (2) a high thrombus burden (HTB) group and a low thrombus burden (LTB) group. Meanwhile, 48 healthy volunteers were recruited as controls. Plasma ox-HDL and gly-ApoA-I concentrations were measured on admission and 7?days after admission.

Results: Higher concentrations of ox-HDL and gly-ApoA-I were found in the STEMI group than in the control group on admission and at d7. Further subgroup analysis showed that ox-HDL and gly-ApoA-I were higher in the SH group than in the no SH group at both time points; the HTB group had higher ox-HDL and ox-HDL/HDL-C levels than the LTB group on admission and at d7. However, gly-ApoA-I and the relative intensity of ApoA-I glycation showed no significant differences between the HTB and LTB groups.

Conclusions: The present data indicate that: (1) SH is associated with increased plasma concentrations of ox-HDL and gly-ApoA-I and therefore aggressive treatment is recommended; and (2) that ox-HDL and ox-HDL/HDL-C were higher in the HTB group and may be used to quantify thrombus burden.     

Pancreatic B-cell function is altered by oxidative stress induced by acute hyperglycaemia.

AIMS: Type 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading. METHODS: We calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes]. RESULTS: Thioredoxin levels decreased after glucose loading [66.1 +/- 23.7, *59.3 +/- 22.4, *49.3 +/- 21.2 and *37.7 +/- 18.0 ng/ml, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 +/- 0.123, *0.440 +/- 0.120, 0.362 +/- 0.119 and 0.355 +/- 0.131 ng/ml, *P < 0.05 vs. fasting, P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min. CONCLUSIONS: Hyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.