Inhibiting or Antagonizing Glucagon: A Progress in Diabetes Care ?
LEFEBVRE, Pierre ; Paquot, Nicolas ; Scheen, André
in Diabetes, obesity & metabolism (2015)
Absolute or relative hyperglucagonemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet alpha-cells is ... [more ▼]
Absolute or relative hyperglucagonemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet alpha-cells is a direct consequence of intra-islet insulin secretory defects. Recent studies have demonstrated that knock-out of the glucagon receptor or administration of a monoclonal specific glucagon receptor antibody make insulin deficient type 1 diabetic rodents thrive without insulin. These observations suggest that glucagon plays an essential role in the pathophysiology of diabetes and that targeting the alpha-cell and glucagon are innovative approaches in the management of diabetes. Despite active research and identification of promising compounds, no one selective glucagon antagonist is presently used in the treatment of diabetes. Interestingly, besides insulin, several drugs used today in the management of diabetes appear to exert their effects in part by inhibiting glucagon secretion (GLP-1 receptor agonists, DPP-4 inhibitors, alpha glucosidase inhibitors and, maybe, sulfonylureas) or glucagon action (metformin). The potential risks associated with total glucagon suppression include alpha-cell hyperplasia, increased mass of the pancreas, increased susceptibility to hepatosteatosis and hepatocellular injury and increased risk of hypoglycaemia and should be considered in the search and development of new compounds reducing glucagon receptor signalling. In conclusion, more than 40 years after its initial description, the hyperglucagonemia of diabetes can no longer be ignored or minimized and its correction represents an attractive way for improving diabetes management. [less ▲]Detailed reference viewed: 23 (2 ULg)
Prevention cardio-vasculaire: la "polypill", une solution pour vaincre l'inertie clinique et le manque d'observance?
Scheen, André ; Lefebvre, Pierre ; Kulbertus, Henri
in Revue Médicale de Liège (2010), 65(5-6), 267-72
The concept of "polypill" for cardiovascular prevention was introduced in 2003 in a landmark paper of the British Medical Journal. A model based on results provided by evidence-based medicine suggested ... [more ▼]
The concept of "polypill" for cardiovascular prevention was introduced in 2003 in a landmark paper of the British Medical Journal. A model based on results provided by evidence-based medicine suggested that a "polypill", that contains a statin, three blood pressure lowering drugs (each at half standard dose), aspirin and folic acid, would result in an 80% reduction in the incidence of coronary and cerebrovascular events, while being associated with a good tolerance profile and offering a favourable cost-effectiveness ratio. The present paper aims at presenting the new advances dealing with this new paradigm in cardiovascular prevention. We will present the progresses of the "polypill" concept since 2003, the results of a first controlled clinical trial, the pharmaceutical feasibility for routine clinical use and the potential pharmaco-economical impacts of such a strategy. The "polypill" may offer a solution to avoid physician's clinical inertia and reduce patients's lack of compliance, two drawbacks in the field of cardiovascular prevention. [less ▲]Detailed reference viewed: 129 (1 ULg)
Les cas cliniques, une vision panachee de la medecine: de la simple anecdote a l'enseignement pratique.
Lefebvre, Pierre ; Scheen, André
in Revue Médicale de Liège (2009), 64(7-8), 357Detailed reference viewed: 33 (4 ULg)
Insuline glargine et cancer: une tempete dans un verre d'eau?
Scheen, André ; Lefebvre, Pierre
in Revue Médicale de Liège (2009), 64(9), 440-5
Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk ... [more ▼]
Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of cancer, especially breast cancer, in patients with type 2 diabetes. The present article aims at briefly presenting the state of the art based upon currently available data. We will first summarize the observations reported in recent publications, then we will present a critical analysis of these in fact non-conclusive findings, and finally we will conclude with some practical recommendations. [less ▲]Detailed reference viewed: 73 (1 ULg)
L'etude clinique du mois. United Kingdom Prospective Diabetes Study: 10 ans plus tard.
Scheen, André ; Paquot, Nicolas ; Lefebvre, Pierre
in Revue Médicale de Liège (2008), 63(10), 624-9
A 10-year post-trial monitoring of patients with newly diagnosed type 2 diabetes randomised in the "United Kingdom Prospective Diabetes Study" (UKPDS) demonstrated a continued reduction in microvascular ... [more ▼]
A 10-year post-trial monitoring of patients with newly diagnosed type 2 diabetes randomised in the "United Kingdom Prospective Diabetes Study" (UKPDS) demonstrated a continued reduction in microvascular risk (-24%, p = 0.001) and emergent risk reductions for myocardial infarction (-15%, p = 0.01) and death from any cause (-13%, p = 0.007), despite an early loss of glycaemic differences ("legacy effect"). A continued benefit after metformin therapy was evident during the ten-year post-trial follow-up among overweight patients (-33%, p = 0.005 for myocardial infarction and -27%, p = 0.002 for death from any cause). In contrast, the benefits of previously improved blood pressure control were not sustained when between-groups differences in blood pressure were lost during follow-up, except for a reduced risk for peripheral vascular disease. These observations are strong arguments in favour of an early optimisation of blood glucose control and of a sustained control of blood pressure in patients with type 2 diabetes. [less ▲]Detailed reference viewed: 152 (5 ULg)
Le cerveau, un organe gluco-dependant. Effets deleteres de l'hypoglycemie et de l'hyperglycemie.
Radermecker, Régis ; Philips, Jean-Christophe ; Jandrain, Bernard et al
in Revue Médicale de Liège (2008), 63(5-6), 280-6
Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and ... [more ▼]
Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and progress to a coma. Hypoglycaemic coma, the most common one, has a pure metabolic origin (neuroglucopenia) whereas hyperglycaemic coma is more complex and mainly due to osmotic disturbances. Besides acute changes of plasma glucose concentrations, it is generally recognized that more subtle chronic or recurrent glucose abnormalities could also result in brain dysfunction. However, such clinical consequences are more difficult to assess in clinical practice. Nevertheless, learning perturbations in young patients with type 1 diabetes and memory losses, sometimes severe and subject to progress to dementia ("diabetic encephalopathy") in older type 1 or type 2 diabetic patients, have been reported, although with some controversy. The present paper summarizes the current knowledge of both acute and chronic cerebral dysfunctions following perturbations of blood glucose levels in diabetic patients. [less ▲]Detailed reference viewed: 641 (11 ULg)
ACE I/D polymorphism predicts end stage renal disease and or mortality in type I diabetic patients except for those with already advanced nephropathy: the follow up of the Genesis/Genediab Studies
; ; et al
in Diabetologia (2007, September), 50(Suppl. 1), 157-158Detailed reference viewed: 23 (0 ULg)
Ericksonian hypnosis in tinnitus therapy.
Maudoux, Audrey ; Bonnet, Sophie ; et al
in B-ENT (2007), 3 Suppl 7
OBJECTIVE: To evaluate the effect of Ericksonian therapy on tinnitus STUDY DESIGN: Non-randomised, prospective longitudinal study. SETTING: Tertiary referral centre. PATIENTS: A total of 49 patients ... [more ▼]
OBJECTIVE: To evaluate the effect of Ericksonian therapy on tinnitus STUDY DESIGN: Non-randomised, prospective longitudinal study. SETTING: Tertiary referral centre. PATIENTS: A total of 49 patients underwent hypnosis therapy. Fourteen patients failed to finish the therapy (drop-out rate: 35%). Of the 35 patients who completed the therapy, 20 were male and 15 female. The average age was 46.3 years (range 17-78). INTERVENTION: The treatment is based on the principles and approaches of Ericksonian hypnosis. The first session was mainly dedicated to the evaluation of the impact of tinnitus on the patient's life and to an explanation of hypnosis therapy. The next sessions were "learning sessions" based on relaxation and mental imaging. Exercises were first based on all senses other than hearing. Then they focused on hearing, teaching patients how to modulate sound intensity, and finally how to modulate tinnitus intensity. Patients also learnt self-hypnosis. MAIN OUTCOME MEASURE(S): To evaluate the effect of the treatment, tinnitus was assessed with the Tinnitus Handicap Inventory questionnaire before and after the therapy. Results: After 5 to 10 sessions (mean: 8.09 + -1.92) of Ericksonian hypnosis therapy, the 35 patients were capable of self-hypnosis with the aim of modulating their tinnitus, and the measured THI score fell for all patients. The global score improved significantly from 60:23 before EH therapy to 16.9 at discharge. Within the group, the initial score was distributed as follows: 0% slight, 14% mild, 31% moderate, 31% severe and 23% catastrophic. The t-test for dependent variables revealed significant improvements in all subgroups (p < or = 0.005). CONCLUSIONS: The results of this clinical trial demonstrate that Ericksonian hypnosis, in particular using self-hypnosis, is a promising technique for treating patients with tinnitus. [less ▲]Detailed reference viewed: 58 (4 ULg)
Actualites therapeutiques en diabetologie
Paquot, Nicolas ; ; Radermecker, Régis et al
in Revue Médicale de Liège (2007), 62(5-6, May-Jun), 317-23
The recent epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can reduce morbidity have made the effective treatment of hyperglycemia a priority. The new therapeutic ... [more ▼]
The recent epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can reduce morbidity have made the effective treatment of hyperglycemia a priority. The new therapeutic agents and the development of algorithms for the adjustment of therapy might contribute to an improved management of the disease. Moreover, type 2 diabetes is frequently associated with other co-morbidities (obesity, hypertension, dyslipidaemia, prothrombotic state). The appropriate management of patients with type 2 diabetes requires a global approach targeting each risk factor in order to reduce cardiovascular morbidity and mortality. This challenge represents a major public health issue. In type 1 diabetes patients, intensive therapy such as in the Diabetes Control and Complications Trial (DCCT) has been shown to obtain long-term beneficial effects on the reduction of the risk of progressive retinopathy, neuropathy and nephropathy and of the risk of cardiovascular disease. This benefit reinforces the original DCCT message that intensive therapy should be implemented as early as possible in people with type 1 diabetes. The recent development of new insulin analogues and the technical improvements of portable insulin pumps might contribute to obtain such a better metabolic control. [less ▲]Detailed reference viewed: 75 (4 ULg)
Comment j'explore...le syndrome metabolique par sa nouvelle definition dite de "consensus".
Scheen, André ; Luyckx, Françoise ; Lefebvre, Pierre
in Revue Médicale de Liège (2006), 61(1), 48-52
The International Diabetes Federation recently proposed a so-called consensus definition of metabolic syndrome. According to this new definition, a subject has the metabolic syndrome if he/she has ... [more ▼]
The International Diabetes Federation recently proposed a so-called consensus definition of metabolic syndrome. According to this new definition, a subject has the metabolic syndrome if he/she has abdominal obesity (considered as a prerequisite and assessed, in the European population, by a waist circumference > 80 cm in women and > 94 cm in men) and, in addition, at least two other risk factors among 1) elevated fasting triglycerides > or = 150 mg/dl; 2) low HDL cholesterol HDL < 50 mg/dl in women and < 40 mg/dl in men; 3) increased arterial blood pressure > or = 130/ 85 mm Hg; and 4) elevated fasting plasma glucose concentration > or = 100 mg/dl. We will discuss the advantages and limitations of this new definition as well as the consequences of its use on the prevalence of the metabolic syndrome in the Belgian population. [less ▲]Detailed reference viewed: 321 (4 ULg)
L'etude Proactive: prevention secondaire des accidents cardio-vasculaires par la pioglitazone chez le patient diabetique de type 2.
Scheen, André ; Lefebvre, Pierre
in Revue Médicale de Liège (2005), 60(11), 896-901
PROactive is a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. Patients were assigned to oral pioglitazone titrated from 15 mg to ... [more ▼]
PROactive is a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. Patients were assigned to oral pioglitazone titrated from 15 mg to 45 mg or matching placebo, to be taken in addition to their glucose-lowering drugs and other medications. After a mean follow up of 34.5 months, pioglitazone reduced the composite of all-cause mortality, non-fatal myocardial infarction, and stroke (intention to treat analysis: hazard ratio = 0.84; 95% CI: 0.72-0.98; p = 0.027). Various favourable metabolic effects could contribute to this cardiovascular protection, i.e. an absolute 0.5 % reduction in HbA1c, a 9% increase in HDL cholesterol, a 13% decline of triglycerides, and a 3 mm Hg reduction in systolic blood pressure in the pioglitazone group compared to placebo. The requirement of insulin was reduced by almost 50% in the pioglitazone group as compared to the placebo group. The incidence of cases of oedema and congestive heart failure was higher in the pioglitazone group. In conclusion, in patients with type 2 diabetes who are at high cardiovascular risk, pioglitazone improves cardiovascular outcome, and reduces the need to add insulin to glucose-lowering regimens compared to placebo. [less ▲]Detailed reference viewed: 390 (6 ULg)
Intact cross-talk between insulin secretion and insulin action after postgastroplasty recovery of ideal body weight in severely obese patients.
Letiexhe, Michel ; Desaive, Claude ; Lefebvre, Pierre et al
in International Journal of Obesity & Related Metabolic Disorders (2004), 28(6), 821-3
Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of ... [more ▼]
Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of insulin secretion, action, clearance and inhibition of its own secretion, although the parallel kinetics of all these changes remained questionable. Using the intravenous glucose tolerance test, we demonstrated a full normalization of insulin secretion, action on glucose metabolism and clearance in eight obese women who recovered and maintained ideal body weight following gastroplasty. Reciprocal changes were observed between postglucose acute insulin secretion and insulin-mediated glucose disposal so that the so-called disposition index (product of these two variables) remained unchanged after vs before gastroplasty in those individuals with normal glucose tolerance. These favourable results should encourage obtaining a drastic and sustained weight loss in patients with severe obesity at risk of developing type II diabetes. [less ▲]Detailed reference viewed: 22 (2 ULg)
L'hypoglycemie reactive: un phenomene critique mysterieux, insidieux, mais non dangereux.
Scheen, André ; Lefebvre, Pierre
in Revue Médicale de Liège (2004), 59(4), 237-42
Numerous individuals complain of malaise attributed to hypoglycaemia. However, the diagnosis of hypoglycaemia is rarely documented and most often overstated. Reactive hypoglycaemia in the postprandial ... [more ▼]
Numerous individuals complain of malaise attributed to hypoglycaemia. However, the diagnosis of hypoglycaemia is rarely documented and most often overstated. Reactive hypoglycaemia in the postprandial state is rather exceptional. The diagnosis relies upon the measurement of plasma glucose concentration (< 3 mmol/l or 55 mg/dl) at the time of the malaise. Reactive hypoglycaemia is generally associated with adrenergic symptoms and, less often, with cognitive disturbances. Importantly, a plasma glucose concentration below 3 mmol/l during an oral glucose tolerance test is not sufficient to decide that the patient suffers from reactive hypoglycaemia. Treatment is based on dietary advices including frequent small split meals and limitation of carbohydrates with high glycaemic index. Acarbose, a specific inhibitor of gut alpha-glucosidase enzymes, may be helpful in case of diet failure. As compared with true reactive hypoglycaemia, a postprandial hyperadrenergic reaction without real concomitant hypoglycaemia is much more prevalent. Careful anamnesis may suspect such a diagnosis, but other diagnoses such as panic attack or vasovagal reaction should be excluded. Treatment is purely symptomatic and essentially empiric. [less ▲]Detailed reference viewed: 358 (0 ULg)
Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic control
; ; Albert, Adelin et al
in Diabetic Medicine : A Journal of the British Diabetic Association (2003), 20(7), 580-585
Aims The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) greater than or equal to 40 mg/24 h] from baseline covariates in Type 1 diabetic ... [more ▼]
Aims The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) greater than or equal to 40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC). Methods Based on material from the Diabetes Control and Complications Trial study (n = 1441), patients were considered as under good or poor MC if their HbA(1c) mean level up to last visit fell in the lowest (less than or equal to 6.9%) or highest (greater than or equal to 9.5%) quintile of the overall HbA(1c) distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data. Results Among patients with good MC (n = 277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n = 268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P < 0.0001), AER (P < 0.001), duration of diabetes (P < 0.005), body mass index (BMI) (P < 0.005), all at baseline, and to gender (P < 0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC. Conclusions This study confirms occurrence of diabetic nephropathy under good MC and non-occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC. [less ▲]Detailed reference viewed: 23 (0 ULg)
A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism.
Gaspard, Ulysse ; Scheen, André ; et al
in Contraception (2003), 67(6), 423-9
In this open-label, randomized study we compared the influence of a new oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin) with a reference preparation containing 30 ... [more ▼]
In this open-label, randomized study we compared the influence of a new oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin) with a reference preparation containing 30 microg ethinylestradiol and 150 microg desogestrel (Marvelon) on variables of carbohydrate metabolism by means of oral glucose tolerance tests at baseline and in the 6th and 13th treatment cycle. The mean levels of fasting glucose and insulin were similar at baseline and after 13 treatment cycles, whereas C-peptide and free fatty acid levels decreased slightly in both groups. All blood glucose and insulin values measured in the oral glucose tolerance tests were within normal ranges, despite a slight increase in the mean areas under the curves of 0-3 h [AUCs (0-3 h)] of both variables from baseline to treatment cycle 13. Differences between both treatments were not statistically significant. The mean AUCs (0-3 h) for C-peptide were not markedly changed in any treatment group. Free fatty acid levels decreased by 42% in the drospirenone group and increased by 48.9% in the desogestrel group, in terms of means of individual changes. Both preparations were well tolerated and equally efficacious regarding contraception and cycle control. The mean body weight was slightly decreased in most cycles during treatment with the drospirenone combination, as compared to baseline, while it was slightly increased versus baseline in all cycles during treatment with the desogestrel combination. The combination with drospirenone had less impact on blood pressure than the combination with desogestrel. In conclusion, Yasmin, a combined low-dose oral contraceptive with 30 microg ethinylestradiol and 3 mg of the novel progestogen drospirenone, as well as the reference Marvelon, containing 30 microg ethinylestradiol and 150 microg desogestrel had little impact on carbohydrate metabolism when used for 1 year. The observed changes were small and not suggestive of a clinically relevant deterioration of carbohydrate metabolism. [less ▲]Detailed reference viewed: 54 (3 ULg)
Comment je previens ... les maladies cardio-vasculaires par une approche pharmacologique combinee: y a-t-il place pour une polypill"?"
Scheen, André ; Lefebvre, Pierre ; Kulbertus, Henri
in Revue Médicale de Liège (2003), 58(9), 527-33
In the June 28, 2003 issue of the British Medical Journal, an extensive literature survey based on various large meta-analyses of the efficacy and safety of the reduction of four cardiovascular risk ... [more ▼]
In the June 28, 2003 issue of the British Medical Journal, an extensive literature survey based on various large meta-analyses of the efficacy and safety of the reduction of four cardiovascular risk factors (cholesterol, arterial blood pressure, platelet aggregation, homocysteine) leads to the conclusion that a combined pharmacological intervention should reduce ischaemic heart disease events by 88% and strokes by 80% in at risk individuals. Therefore, a new paradigm is proposed for the prevention of cardiovascular diseases. This new strategy would consist in the systematic prescription to people with a history of heart attack or stroke, those with any form of obliterative atherosclerotic vascular disease or diabetes, and everyone aged 55 and older of a fixed combination of 6 pharmacological agents independently of initial risk factor profile.... Such pharmacological formulation, called "polypill", should contain a statin, three blood pressure lowering drugs (each at half standard dose), aspirin (75 mg/day) and folic acid (0.8 mg/day). We discuss the pros and cons of this new paradigm. However, the efficacy of such "polypill" remains to be demonstrated in a large controlled clinical trial as well as its superiority as compared to a classical approach of cardiovascular prevention based upon the individual optimal correction of each risk factor thanks a dose titration of each pharmacological compound. [less ▲]Detailed reference viewed: 595 (0 ULg)
Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism.
; Gaspard, Ulysse ; Demeyer, Fabienne et al
in Contraception (2002), 66(6), 411-5
This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women ... [more ▼]
This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-microg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel. [less ▲]Detailed reference viewed: 51 (3 ULg)
Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients.
Paquot, Nicolas ; Scheen, André ; et al
in Obesity Research (2002), 10(3), 129-34
OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH ... [more ▼]
OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH METHODS AND PROCEDURES: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion. RESULTS: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-(2)H(2)-glucose) and total glucose output (measured with 2-(2)H(1)-glucose) were approximately 30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia. DISCUSSION: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance. [less ▲]Detailed reference viewed: 26 (1 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: 56 (0 ULg)