Weight Management in Type 2 Diabetes: Current and Emerging Approaches to Treatment.
; Scheen, André
in Diabetes care (2015), 38(6), 1161-1172
Diabetes is a growing global health concern, as is obesity. Diabetes and obesity are intrinsically linked: obesity increases the risk of diabetes and also contributes to disease progression and ... [more ▼]
Diabetes is a growing global health concern, as is obesity. Diabetes and obesity are intrinsically linked: obesity increases the risk of diabetes and also contributes to disease progression and cardiovascular disease. Although the benefits of weight loss in the prevention of diabetes and as a critical component of managing the condition are well established, weight reduction remains challenging for individuals with type 2 diabetes due to a host of metabolic and psychological factors. For many patients, lifestyle intervention is not enough to achieve weight loss, and alternative options, such as pharmacotherapy, need to be considered. However, many traditional glucose-lowering medications may lead to weight gain. This article focuses on the potential of currently available pharmacological strategies and on emerging approaches in development to support the glycemic and weight-loss goals of individuals with type 2 diabetes. Two pharmacotherapy types are considered: those developed primarily for blood glucose control that have a favorable effect on body weight and those developed primarily to induce weight loss that have a favorable effect on blood glucose control. Finally, the potential of combination therapies for the management of obese patients with type 2 diabetes is discussed. [less ▲]Detailed reference viewed: 8 (0 ULg)
Pulsatile stress in middle-aged patients with Type 1 or Type 2 diabetes compared to nondiabetic controls.
Philips, Jean-Christophe ; Marchand, Monique ; Scheen, André
in Diabetes Care (2010), 33(11), 2424-2429
AbstractBackground: Arterial pulse pressure (PP) is considered as an independent cardiovascular risk factor. We compared PP during an active orthostatic test in middle-aged patients with type 1 diabetes ... [more ▼]
AbstractBackground: Arterial pulse pressure (PP) is considered as an independent cardiovascular risk factor. We compared PP during an active orthostatic test in middle-aged patients with type 1 diabetes and with type 2 diabetes, and corresponding nondiabetic controls. Methods: 40 patients with type 1 diabetes (mean age 50 years, diabetes duration 23 years, BMI 23.0 kg/m(2)) were compared to 40 non hypertensive patients with type 2 diabetes (respectively, 50 years, 8 years, 29.7 kg/m(2)). Patients taking antihypertensive agents or with renal insufficiency were excluded. All patients were evaluated with a continuous noninvasive arterial blood pressure monitoring (Finapres(R)) in standing (1 min), squatting (1 min) and again standing position (1 min). Patients with type 1 or type 2 diabetes were compared with two groups of 40 age-, sex- and BMI-matched healthy subjects. Results: Patients with type 1 diabetes and patients with type 2 diabetes showed significantly higher PP, heart rate (HR) and PPxHR double product (type 1 : 5263 vs 4121 mmHg/min, p=0.0004; type 2 : 5359 vs 4321 mmHg, p=0.0023) levels than corresponding controls. There were no significant differences between patients with type 1 diabetes and type 2 diabetes regarding PP (59 vs 58 mmHg), HR (89 vs 88/min), and PPxHR product (5263 vs 5359 mmHg/min). Conclusion: Patients with type 1 diabetes have comparable increased levels of peripheral PP, an indirect marker of arterial stiffness, and PPxHR, an index of pulsatile stress, as non-hypertensive patients with type 2 diabetes at similar mean age of 50 years. [less ▲]Detailed reference viewed: 51 (1 ULg)
Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program.
; ; et al
in Diabetes Care (2008), 31 Suppl 2
OBJECTIVE: To better define the efficacy and safety of rimonabant, the first selective cannabinoid type 1 (CB(1)) receptor antagonist, in a large population of overweight and obese patients using pooled ... [more ▼]
OBJECTIVE: To better define the efficacy and safety of rimonabant, the first selective cannabinoid type 1 (CB(1)) receptor antagonist, in a large population of overweight and obese patients using pooled efficacy data from three Phase III nondiabetes Rimonabant in Obesity and Related Metabolic Disorders (RIO) studies, selected efficacy data from the RIO-Diabetes study, and pooled safety data for all four RIO studies. RESEARCH DESIGN AND METHODS: The RIO studies enrolled patients who were either overweight (BMI >27 kg/m(2)) with at least one comorbidity (i.e., hypertension, dyslipidemia, or, for RIO-Diabetes, type 2 diabetes) or obese. All patients received daily treatment with rimonabant (5 or 20 mg) or placebo for 1 year plus a hypocaloric diet (600 kcal/day deficit) and advice on increased physical activity. RIO-Europe (n = 1,508), RIO-North America (n = 3,045), and RIO-Lipids (n = 1,036) excluded patients with type 2 diabetes; untreated dyslipidemia was an entry requirement for RIO-Lipids. RIO-Diabetes (n = 1,047) required the presence of type 2 diabetes inadequately controlled by sulfonylurea or metformin monotherapy. RESULTS: The pooled intention-to-treat population comprised 5,580 patients without diabetes (3,165 completed treatment) and 1,047 patients with diabetes (692 completed treatment). Most efficacy measures improved during the 4-week placebo run-in period, except that HDL cholesterol decreased as expected in the early phase of a hypocaloric diet. After 1 year of randomized treatment, changes from baseline with 20 mg rimonabant in the nondiabetic population were as follows: body weight -6.5 kg, waist circumference -6.4 cm, HDL cholesterol +16.4%, triglycerides -6.9%, fasting insulin -0.6 muU/ml, and homeostasis model assessment for insulin resistance (HOMA-IR) -0.2 (all P < 0.001 vs. placebo). In the diabetic population, 20 mg rimonabant reduced A1C levels by 0.6% (P < 0.001 vs. placebo). Regression analysis of change in HDL cholesterol, triglycerides, adiponectin (in RIO-Lipids), and A1C (in RIO-Diabetes) versus body weight at 1 year by ANCOVA suggested that 45-57% of the effect of rimonabant could not be explained by the observed weight loss. At 1 year, adverse events more frequently reported with rimonabant were gastrointestinal, neurological, and psychiatric in nature. Serious adverse events were infrequent and almost equivalent to placebo. Overall discontinuation rates were similar across treatment groups, except discontinuation from adverse events, which occurred more frequently with 20 mg rimonabant versus placebo (most commonly, depressive disorders [1.9 vs. 0.8%], nausea [1.4 vs. 0.1%], mood alterations with depressive symptoms [1.0 vs. 0.6%], and anxiety [1.0 vs. 0.3%]). A thorough review of psychiatric and neurological adverse events was performed. CONCLUSIONS: In overweight/obese patients, 20 mg/day rimonabant produced weight loss and significant improvements in multiple cardiometabolic risk factors such as waist circumference, A1C, HDL cholesterol, and triglycerides. Rimonabant was generally well tolerated, with more frequently reported adverse events being gastrointestinal, neurological, and psychiatric in nature. [less ▲]Detailed reference viewed: 32 (3 ULg)
Squatting amplifies pulse pressure increase with disease duration in patients with type 1 diabetes.
Philips, Jean-Christophe ; Marchand, Monique ; Scheen, André
in Diabetes Care (2008), 31(2), 322-4
OBJECTIVE: To evaluate pulse pressure changes according to duration of type 1 diabetes and to assess the influence of posture. RESEARCH DESIGN AND METHODS: We performed continuous measurement of blood ... [more ▼]
OBJECTIVE: To evaluate pulse pressure changes according to duration of type 1 diabetes and to assess the influence of posture. RESEARCH DESIGN AND METHODS: We performed continuous measurement of blood pressure with a Finapres device during a 3 x 1 min posture test (standing, squatting, standing) in 159 type 1 diabetic patients divided into four groups according to diabetes duration (<or=10, 11-20, 21-30, and >30 years, groups 1-4, respectively) and compared the results with those of age-matched nondiabetic subjects. RESULTS: Pulse pressure progressively increased according to type 1 diabetes duration (P < 0.0001), especially in women, but not in age-matched nondiabetic subjects (NS). Pulse-pressure increase from group 1 to group 4 was amplified in the squatting position (from 50 +/- 17 to 69 +/- 14 mmHg) compared with standing (from 44 +/- 15 to 55 +/- 12 mmHg). CONCLUSIONS: Pulse pressure increases according to type 1 diabetes duration more in women than in men, and the squatting position sensitizes such pulse-pressure increase in both sexes. [less ▲]Detailed reference viewed: 64 (3 ULg)
Reversibility of antipsychotic treatment-related diabetes in patients with schizophrenia - A case series of switching to aripiprazole
; ; et al
in Diabetes Care (2006), 29(10), 2329-2330Detailed reference viewed: 9 (0 ULg)
Diabetes does not influence treatment decisions regarding revascularization in patients with stable coronary artery disease
; ; et al
in Diabetes Care (2006), 29(9), 2003-2011
OBJECTIVE - To evaluate whether in stable angina preference for coronary revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is influenced by ... [more ▼]
OBJECTIVE - To evaluate whether in stable angina preference for coronary revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is influenced by diabetes status and whether this has prognostic implications. RESEARCH DESIGN AND METHODS - A total of 2,928 consecutive patients with stable angina who were enrolled in the prospective Euro Heart Survey on Coronary Revascularization were studied. Multivariable analyses were applied to evaluate the relation between diabetes, treatment decision, and 1-year outcome. RESULTS - Diabetes was documented in 587 patients (20%) who had more extensive coronary disease. Revascularization was intended in 74% of patients with diabetes and in 77% of those without diabetes. In patients selected for revascularization, CABG was intended in 35% of diabetic and in 33% of nondiabetic patients. Multivariable analyses did not change these findings, but in some subgroups diabetes influenced treatment decisions. For example, diabetic subjects with mild heart failure had more often intended revascularization (91%) than those without diabetes (67%, P < 0.001). Treatment decisions in patients with more extensive (left main, multivessel, or proximal left anterior descending artery) disease were not influenced by diabetes status. Diabetes was not associated with an increased incidence of all-cause death, nonfatal cerebrovascular accident, or nonfatal myocardial infarction at 1 year, regardless of preferred treatment. The incidence of the combined end points was 7.3% in diabetic and 6.8% in nondiabetic patients (adjusted hazard ratio 1.0 [95% CI 01.7-1.41]). CONCLUSIONS - in stable angina, treatment decisions regarding revascularization or the choice for CABG or PCI were not influenced by the presence of diabetes. Diabetes was not associated with a poor prognosis. [less ▲]Detailed reference viewed: 7 (0 ULg)
Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy
; ; et al
in Diabetes Care (2004), 27(11), 2661-2668
OBJECTIVE- Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin ... [more ▼]
OBJECTIVE- Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS- The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS- The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c) (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS- Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy. [less ▲]Detailed reference viewed: 10 (0 ULg)
Diabetes is still a risk factor for restenosis after drug-eluting stent in coronary arteries.
Scheen, André ; Warzee, Fabian
in Diabetes Care (2004), 27(7), 1840-1Detailed reference viewed: 7 (0 ULg)
Preventing, delaying, or masking type 2 diabetes with metformin in the diabetes prevention program?
in Diabetes Care (2003), 26(9), 27012701-3Detailed reference viewed: 8 (0 ULg)
Potential pharmacokinetics interference between alpha-glucosidase inhibitors and other oral antidiabetic agents.
Scheen, André ; Lefebvre, Pierre
in Diabetes Care (2002), 25(1), 247-8Detailed reference viewed: 51 (0 ULg)
Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes.
Scheen, André ; Lefebvre, Pierre
in Diabetes Care (1999), 22(9), 1568-77
Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts ... [more ▼]
Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts an antihyperglycemic activity in a dose-dependent manner between 200 and 600 mg/day in type 2 diabetic patients treated with diet alone, sulfonylureas, or insulin. Additive antihyperglycemic effect may also be obtained by combining troglitazone and metformin. The antihyperglycemic effect of troglitazone as monotherapy is rather modest (reduction of HbA1c by 0.5-1.0%), but it appears to be somewhat greater when it is combined with other antidiabetic drugs. No double-blind studies have directly compared the activity of troglitazone with that of sulfonylureas or metformin. Troglitazone has been shown to exert additional beneficial effects on serum lipid profile and arterial blood pressure. It may be considered as a valuable alternative in insulin-resistant (obese and hyperinsulinemic) diabetic patients who appear to be the best responders to the drug. However, the efficacy of troglitazone is challenged by its safety profile, and the risk of hepatotoxicity still remains a major concern in clinical practice. [less ▲]Detailed reference viewed: 22 (0 ULg)
Cardiac autonomic dysfunction in diabetic children.
; ; et al
in Diabetes care (1999), 22(11), 1845-50
OBJECTIVE: Adults with type 1 diabetes may have abnormal alterations in heart rate variability (HRV) due to cardiac autonomic neuropathy. This prospective study was performed to determine whether HRV can ... [more ▼]
OBJECTIVE: Adults with type 1 diabetes may have abnormal alterations in heart rate variability (HRV) due to cardiac autonomic neuropathy. This prospective study was performed to determine whether HRV can be used to detect subclinical autonomic neuropathy in diabetic children. RESEARCH DESIGN AND METHODS: We examined five time domain and three frequency domain HRV indices determined from 24-h Holter recordings in 73 diabetic children and adolescents aged 3-18 years (mean 12.1 years) with a mean duration of diabetes of 55 months. The measures were compared with normal ranges. Z scores were established for each parameter and were compared with classic risk factors of other diabetic complications. RESULTS: Most HRV indices were significantly depressed in children aged > or = 11 years, and the levels of HRV abnormalities were significantly correlated with long-term metabolic control (mean GHb for 4 years) in that age-group. In younger patients, HRV indices were within the normal range and were not correlated with the level of metabolic control. Illness duration and microalbuminuria but not short-term metabolic control (most recent GHb) were also independently predictive of HRV abnormalities. CONCLUSIONS: These results suggest that early puberty is a critical period for the development of diabetic cardiac autonomic dysfunction. Therefore, all type 1 diabetic patients should be screened for this complication by HRV analysis beginning at the first stage of puberty regardless of illness duration, microalbuminuria, and level of metabolic control. [less ▲]Detailed reference viewed: 10 (0 ULg)
Detection of early sympathetic cardiovascular neuropathy by squatting test in NIDDM.
; ; et al
in Diabetes Care (1994), 17(2), 149-51
OBJECTIVE--To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--Three ... [more ▼]
OBJECTIVE--To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--Three groups of nonsmoking, nonobese subjects were studied: 10 healthy subjects, 10 NIDDM patients without autonomic neuropathy (AN), and 10 NIDDM patients with AN defined by the presence of a pathological deep-breathing value. All subjects were given three postural tests: lying-to-standing, sitting-to-standing, and squatting test. Heart rate (HR) and finger arterial pressure were recorded with a noninvasive technique. RESULTS--Blood pressure (BP) fall (expressed as decremental area) was not significantly different among the groups at standing up after sitting or lying. By contrast, a significantly greater BP drop occurred in NIDDM patients with AN (1,123 +/- 245 mm2) compared with NIDDM patients without AN (460 +/- 232 mm2) or normal subjects (429 +/- 138 mm2, P < 0.001). The HR increase after all the orthostatic maneuvers was smaller in diabetic patients with AN (P < 0.01) compared with that recorded in other groups. Significant correlations were observed between BP fall after squatting and either the expiration:inspiration ratio at deep breathing (r = -0.77, P < 0.001) or the duration of diabetes (r = 0.76, P < 0.001). CONCLUSIONS--The intrinsic orthostatic load of the squatting test, which is greater than conventional postural maneuvers, makes the squatting test an easy and useful test to detect early orthostatic dysregulation in NIDDM. [less ▲]Detailed reference viewed: 22 (0 ULg)
Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine.
Scheen, André ; ; et al
in Diabetes Care (1991), 14(4), 325-32
OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo ... [more ▼]
OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo-controlled crossover trial with 1-wk treatment periods (2 x 15 mg/day d-fenfluramine) was conducted. Twenty obese subjects, 10 with normal oral glucose tolerance and 10 with non-insulin-dependent diabetes mellitus (NIDDM), were all treated with a weight-maintaining diet. Euglycemic-hyperinsulinemic glucose clamps with measurement of glucose kinetics with D-[3-3H]glucose were performed at either two (patients without NIDDM, 0.05 and 0.10 U.kg-1.h-1) or three (patients with NIDDM, 0.05, 0.10, and 0.50 U.kg-1.h-1) insulin delivery rates. RESULTS: In the nondiabetic subjects, no significant changes in any metabolic or hormonal parameter were measured in the basal state or during the clamp despite a slight reduction in body weight (-1.2 +/- 0.5 kg, P less than 0.05). In the diabetic patients, no significant changes in body weight or basal plasma insulin levels were observed, but fasting blood glucose levels (8.0 +/- 0.8 vs. 9.4 +/- 1.1 mM, P less than 0.005) and plasma free fatty acid concentrations (1150 +/- 227 vs. 1640 +/- 184 microM, P less than 0.05) were significantly reduced after d-fenfluramine compared with placebo. During the clamp, insulin metabolic clearance rate (MCR) was similar after both placebo and d-fenfluramine; endogenous (hepatic) glucose production was similarly and almost completely suppressed, whereas glucose disposal was remarkably enhanced after d-fenfluramine (average increase of glucose MCR 35 +/- 12%, P less than 0.02). CONCLUSIONS: Whatever the mechanism(s) involved, a 1-wk treatment with d-fenfluramine induces better blood glucose control and improves insulin sensitivity in obese patients with NIDDM independent of significant weight reduction; this last effect is not present in obese subjects with normal oral glucose tolerance. [less ▲]Detailed reference viewed: 13 (1 ULg)
U-100 insulin gives some protection against metabolic deterioration due to CSII interruption.
Scheen, André ; ; Jandrain, Bernard et al
in Diabetes Care (1987), 10(6), 707-11
We investigated the influence of insulin concentration within the insulin pump on the metabolic and plasma free-insulin changes induced by a 6-h nocturnal interruption of continuous subcutaneous insulin ... [more ▼]
We investigated the influence of insulin concentration within the insulin pump on the metabolic and plasma free-insulin changes induced by a 6-h nocturnal interruption of continuous subcutaneous insulin infusion (CSII) in five C-peptide-negative insulin-dependent diabetic patients with low circulating levels of anti-insulin antibodies. We compared the changes in blood glucose, plasma free fatty acids, 3-hydroxybutyrate, and free insulin during the interruption from 2300 to 0500 h of the Nordisk Infuser loaded with either U-100 or U-20 regular insulin. The decrease in plasma free-insulin levels was slower, resulting in a significantly delayed and smaller increase in blood glucose levels (2.4 +/- 1.6 vs. 7.6 +/- 2.9 mM, P less than .025) when the pump contained U-100 instead of U-20 insulin. Although the increases in levels of plasma free fatty acids were similar in both tests, the rise in plasma 3-hydroxybutyrate levels tended to be reduced with U-100 insulin (414 +/- 139 vs. 639 +/- 67 microM, P less than .10). Thus, our observations indicate that U-100 insulin gives some protection against the metabolic deterioration due to the interruption of CSII so that diabetic patients may be able to remain without the pump for longer periods with concentrated rather than diluted insulin. [less ▲]Detailed reference viewed: 17 (0 ULg)
Prevention of metabolic alterations by insulin supplements administered either before or after 2-h nocturnal interruption of CSII.
Scheen, André ; ; Jandrain, Bernard et al
in Diabetes Care (1987), 10(5), 567-72
To evaluate the efficacy of a bolus insulin injection to prevent the metabolic alterations induced by a 2-h nocturnal interruption of a continuous subcutaneous insulin infusion (CSII), nine type I ... [more ▼]
To evaluate the efficacy of a bolus insulin injection to prevent the metabolic alterations induced by a 2-h nocturnal interruption of a continuous subcutaneous insulin infusion (CSII), nine type I (insulin-dependent) C-peptide-negative diabetic patients were studied from 2200 to 0800 h during two randomized tests. An insulin bolus (2.1 +/- 0.2 U) was administered via the pump either at 2300 h, just before CSII interruption, or at 0100 h, after reactivating the pump at its usual basal rate (1.05 +/- 0.11 U/h). The insulin bolus at 2300 h induced a significant rise in plasma free-insulin levels at 2400 h (+6.9 +/- 1.8 mU/L, P less than .01), resulting in an early and marked fall in blood glucose concentrations between 2300 and 0100 h (-2.7 +/- 0.5 mM, P less than .001), with hypoglycemic values in five patients. The insulin bolus at 0100 h counteracted the fall in plasma free-insulin levels observed between 2300 and 0100 h and significantly increased plasma insulin at 0200 h (+3.2 +/- 0.8 mU/L, P less than .01). Blood glucose concentrations that remained stable during the 2-h arrest of the pump fell significantly between 0100 and 0400 h (-2.1 +/- 0.5 mM, P less than .005). This fall rate was significantly lower than that measured within the 3 h after the insulin bolus given before CSII interruption but significantly higher than that observed in a reference control group of patients whose pump was functioning normally throughout the night.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 8 (0 ULg)
Metabolic alterations after a two-hour nocturnal interruption of a continuous subcutaneous insulin infusion.
Scheen, André ; ; Jandrain, Bernard et al
in Diabetes Care (1984), 7(4), 338-42
In order to evaluate the metabolic consequences of a 2-h nocturnal interruption of continuous subcutaneous insulin infusion (CSII), seven insulin-dependent diabetic patients without residual insulin ... [more ▼]
In order to evaluate the metabolic consequences of a 2-h nocturnal interruption of continuous subcutaneous insulin infusion (CSII), seven insulin-dependent diabetic patients without residual insulin secretion were investigated. The changes in blood glucose, plasma free insulin, glucagon, free fatty acids, and 3-hydroxybutyrate (3 OH-B) concentrations have been compared during two randomized tests carried out either during the normal functioning of a Mill-Hill pump from 10 p.m. to 8 a.m. (1.00 +/- 0.06 U insulin/h, keeping adequate metabolic control) or during the same conditions but with a deliberate arrest of the pump between 11 p.m. and 1 a.m. Considering the value recorded at 11 p.m. as reference, interruption of the insulin infusion resulted in: (1) a rapid (already significant after 1 h) and sustained (maximal fall: --12.5 +/- 2.5 mU/L at 3 a.m.) decrease in plasma free insulin; (2) a delayed (significant after 4 h) and linear rise in blood glucose (maximal increase: + 4.0 +/- 1.3 mmol/L at 5 a.m.); (3) an early (significant at midnight) and prolonged rise in plasma free fatty acids (+ 387 +/- 148 mumol/L at 3 a.m.); (4) a delayed (significant after 3 h) and sustained increase in plasma 3 OH-B (+ 347 +/- 88 mumol/L at 3 a.m.); and (5) no significant changes in plasma glucagon. Thus, a 2-h interruption of CSII in resting nocturnal conditions is sufficient to induce significant, delayed, and sustained metabolic alterations in C-peptide-negative patients despite good baseline blood glucose control. Resetting the pump at its basal rate is insufficient to quickly restore adequate circulating insulin levels and effectively counteract the metabolic disturbances. The efficacy of a bolus insulin injection in these conditions should be evaluated. [less ▲]Detailed reference viewed: 8 (0 ULg)