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Diabetologia 04/2010; 53(4):786-9. · 6.81 Impact Factor
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Diabetic Medicine 07/2008; 25(7):884-5. · 2.90 Impact Factor
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ABSTRACT: The Accelerator hypothesis postulates that Type 1 Diabetes (T1D) and Type 2 Diabetes are mostly the same disorder. Till now, the data testing the hypothesis and the importance of BMI and insulin resistance in the development of T1D comes almost exclusively from childhood. Our study aimed to investigate changes in clinical and metabolic characteristics of young adults at diagnosis of T1D during the last decade in a Mediterranean area. Ninety-three adults (> or =18 years) with newly diagnosed T1D were evaluated from our database. Thirty-one of them were diagnosed in the period 07/1994-1995 (G95), 39 between 07/1998 and 1999 (G99) and 23 in 2003 (G03). Plasma C-peptide measurements were performed before and 6 min after intravenous injection of 1 mg of glucagon. In those subjects with a basal C-peptide > 0.2 nmol/l, insulin resistance was evaluated using the HOMA-2 model. HbAc, GAD, IA2 and insulin autoantibodies were measured. There was not a significant rise in BMI at diagnosis of T1D in young adults admitted to our Hospital. This was also the case when BMI after 4 weeks of diagnosis was considered (23.7 +/- 3.6, 23,6 +/- 2.4 and 23.4 +/- 3.3 kg/m2, G95 G99 and G03, respectively). In the entire group of subjects, we could not observed any relationship between the patients BMI and age at diagnosis. Likewise, we could not observed differences in any of the clinical, immunological or metabolic characteristics. IR was not different between groups (G95 n=18, 0.73 +/- 0.21; G99 n=29, 0.86 +/- 0.33; G3 n=13, 0.66 +/- 0.34) and was not related to the age at diagnosis. In summary, our data collected from young adults with newly diagnosed T1D from a Mediterranean area indicates that the phenotype, including BMI, at the onset of the disease has not substantially varied during the last decade. In spite of our data do not fit with the accelerator hypothesis the postulate could be of interest in a different age group.
Acta Diabetologica 02/2008; 45(2):87-90. · 2.78 Impact Factor
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ABSTRACT: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service.
Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded.
In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII.
CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.
Diabetic Medicine 01/2008; 24(12):1419-23. · 2.90 Impact Factor
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ABSTRACT: The aim was to evaluate and compare the outcome of pregnancies of women with type 1 diabetes (T1D) intensively treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Twenty-nine women with T1D receiving CSII during pregnancy as intensive insulin therapy (27 started CSII during pregnancy planning while 2 started CSII during the 1st month of gestation) were matched for age, duration of T1D, White's classification, BMI before gestation, parity and HbA1c before pregnancy with 29 women treated with MDI. Metabolic control and acute complications were registered including ketoacidosis and severe hypoglycaemic episodes, and the development of hypertension induced by pregnancy and pre-eclampsia. Perinatal mortality, stillbirth, minor and major congenital malformations, macrosomia, weeks at delivery, caesarean section and perinatal complications were also recorded. As expected, there were no differences between the two groups in terms of age, duration of the disease, White's classification, BMI before gestation, parity and HbA1c before pregnancy. The proportion of subjects who received preconceptional guidance and planned pregnancy did not differ between groups. No differences were observed in HbA1c, insulin dose and BMI throughout gestation in either group of patients. Maternal, foetal and perinatal outcome were similar in women treated with CSII or MDI. The use of CSII in pregestational T1D women is associated with similar results in metabolic control, maternal, foetal and perinatal outcome during pregnancy to those obtained using MDI.
Acta Diabetologica 04/2007; 44(1):34-7. · 2.78 Impact Factor
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ABSTRACT: To assess the effects of telecare on the results of intensive follow-up in T1D patients with poor metabolic control.
After initial evaluation, 40 T1D were randomised to either a Telecare (TG) or Conventional Group (CG). Patients had an intensive 6-month follow-up and helped to make decisions concerning treatment self-management. The TG had 12 appointments: 9 telematic with the GlucoBeep system+3 ambulatory. The CG had 12 outpatient appointments. At 0, 6 (end of study) and 12 months, metabolic control, self-management and quality of life were evaluated. Cost analysis was made at study end.
Thirty patients completed the study (16 TG, 14 CG). Intention to treat analysis included 19 TG and 16 CG. Improvement in HbA(1c) was similar in both groups TG: 8.4+/-1.2%; 7.5+/-1.4%; 7.6+/-0.9%, p=0.008; CG: 8.9+/-1.3%; 7.7+/-0.9%; 7.6+/-0.7%, p=0.001; with a decrease in hypoglycaemic events and improvement in self-management and quality of life. Patient costs were lower in the TG versus CG in appointment length (0.25h versus 0.5h). However, 30% of the diabetes team and patient appointments were longer than expected due to technical difficulties: (0.25h versus 1h).
Intensive telematic follow-up achieves similar results to those of intensive face-to-face follow-up with lower patient costs. However, communication technology must be improved.
Diabetes Research and Clinical Practice 11/2006; 74(1):26-32. · 2.75 Impact Factor
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ABSTRACT: We evaluated in a double-blind study the effect of early treatment with the immunomodulatory drug fusidin in patients with newly diagnosed type 1 diabetes mellitus.
Twenty-eight adults with newly diagnosed type 1 diabetes were included in the study. The patients were randomly assigned (computer-generated random number sequence) to two experimental groups. Patients allocated to the fusidin (FUS) group (n=15) received sodium fusidate (fusidin; 500 mg orally three times daily for 4 weeks). Subsequently the drug was given at the same dose and scheduled for two consecutive weeks a month followed by 2 weeks a month without the drug for 20 weeks. Subjects allocated to the placebo (PCB) group (n=13) received placebo according to the same schedule and conditions described for sodium fusidate in the FUS group. All patients received a diet adjusted to their age and BMI, and intensive insulin therapy.
There were no statistically significant differences between the FUS and PCB groups in beta cell function, evaluated by basal and glucagon-stimulated C-peptide values during the follow-up (24 and 48 weeks). There was also no difference between the two groups in insulin requirement after 48 weeks (0.4+/-0.2 and 0.4+/-0.2 U/kg body weight for the FUS and PCB groups, respectively). Antibody titres, including insulin autoantibodies, were similar in the two groups during the follow-up.
Early treatment of newly diagnosed type 1 diabetes patients with intermittently administered fusidin failed to influence the natural course of the disease.
Diabetologia 09/2005; 48(8):1464-8. · 6.81 Impact Factor
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ABSTRACT: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies.
Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed.
No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.
Diabetic Medicine 03/2005; 22(2):137-43. · 2.90 Impact Factor
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ABSTRACT: The aims of the study were to determine whether transforming growth factor beta1 TGF-beta1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose.
Fourteen patients (mean age 24.3 +/- 4.9 years) admitted to hospital for onset of Type 1 diabetes were studied. On the first day of hospitalization, before insulin therapy, and at 1, 4 and 16 weeks, fasting blood glucose, HbA(1c), lipid profile and TGF-beta1 levels and TGF-beta1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group.
Plasma and urinary TGF-beta1 levels were significantly lower in controls (4.7 (1.6-6.8) ng/ml P < 0.001; 5.7 (1.5-8.5) ng/mg urinary creatinine, P < 0.01) than in patients with Type 1 diabetes mellitus [10.5 (1.8-24.9) ng/ml; 10.1 (4.2-29.8) ng/mg urinary creatinine]. On study completion, HbA(1c) fell from 11.6 +/- 2.0 to 5.4 +/- 0.6% (P < 0.001). Improved metabolic control was not associated with changes in plasma (9.4 (2.6-19.5)/5.9 (1.6-21.5)/7.0 (2.3-30.2)/10.5 (1.8-24.9) ng/ml at baseline, 1, 4 and 16 weeks, respectively) or urinary (12.0 (4.7-29.5)/10.9 (1.5-20.5)/8.7 (4.3-16.9)/10.1 (4.2-29.8) ng/mg urinary creatinine) TGF-beta1 levels. A statistically significant correlation was observed between plasma TGF-beta1 and insulin dosage (U/kg/day) (r = 0.52, P = 0.037).
The increased TGF-beta1 production observed herein was not modulated by glycaemic reduction and could be a response to immuno-inflammatory activation present at the onset of Type 1 diabetes.
Diabetic Medicine 09/2004; 21(8):818-22. · 2.90 Impact Factor
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ABSTRACT: Allelic variants of the tumor necrosis factor-alpha (TNF-alpha) gene seem to contribute to insulin resistance increasing the transcription rate of TNF-alpha. The TNF-alpha -863A allele is associated with a lower expression of TNF-alpha gene and less secretion of the cytokine. To investigate whether an abnormal TNF-alpha system regulation may contribute to early impairment of insulin action in first-degree relatives of patients with type 2 diabetes mellitus (DM), we studied the TNF-alpha -863C/A polymorphism and the soluble fraction of TNF-alpha receptor-2 (sTNFR2) concentration in these subjects in comparison to a control group. A total of 52% of subjects in the relatives' group showed an abnormal oral glucose tolerance (either as impaired glucose tolerance [IGT] or diabetes) and had more features of the insulin resistance syndrome, despite showing similar body composition as controls. The plasma concentration of the sTNFR2 was higher and insulin sensitivity (%S) was lower in the relatives' group than in the controls. Likewise, the TNF-alpha -863A allele was more commonly detected in the control group (10 of 41) than in the relative's group (2 of 36, P =.029). In a multivariate linear regression analysis, neither TNF-alpha -863A allele nor sTNFR2 independently determined %S. Only body mass index (BMI) and the presence of a positive family history of DM were independent determinants of insulin resistance. In summary, our study showed a lower rate of TNF-alpha -863A allele and higher concentrations of sTNFR2 in first-degree relatives of DM subjects. These findings could be included among the genetic, metabolic, and clinical heterogeneity that characterizes the pathophysiology of DM. The presence of abnormalities in the TNF-alpha pathway could predispose to the development of DM in subjects at risk for the disease.
Metabolism 09/2003; 52(8):1068-71. · 2.66 Impact Factor
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ABSTRACT: To investigate the effects of atorvastatin on glucose homeostasis, the basal and postprandial lipid profiles and the CRP levels (C reactive protein) in subjects with impaired fasting glucose (IFG).
Thirty-three subjects (22 men and 11 women) were included in our study. All displayed an IFG (fasting plasma glucose between 6.1 and 7.0 mmol/l) on at least two occasions during the last 6 months prior the study. They were randomly assigned to receive either 40 mg atorvastatin/day (n=16) or placebo (n=17) over 16 weeks, in a double-blind design. Before and after the end of the study all participants underwent on three consecutive days: a 75-g oral glucose tolerance test, a frequent sampling intravenous glucose tolerance test with Minimal Model analysis and a meal tolerance test (glucose, insulin and triglycerides). CRP was measured before and after the treatment period.
CRP decreased significantly in the atorvastatin-treated group compared with the placebo group (percent change respect initial values; -42.3 %[-21.5 to - 63.1] and -9.6%[15.0 to -34.0], respectively, p<0.01). Atorvastatin treatment did not produce any change in oral glucose tolerance categories or induce any change in glucose and insulin response in OGTT. The statin produced a trend towards a significant improvement in insulin sensitivity as expressed by a change in Si from baseline to the end of treatment. Atorvastatin reduced the postprandial response of triglycerides to the meal test compared with placebo (19-26 % across the meal test, p<0.05) correlating with the amelioration observed in Si (-0.34, p<0.05; percentage changes).
Our results suggest that the use of statins in subjects with IFG seems to include other potentially beneficial actions in addition to their cholesterol-lowering effects.
Diabetic Medicine 09/2003; 20(9):743-5. · 2.90 Impact Factor
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ABSTRACT: Allelic variants of the tumor necrosis factor-α (TNF-α) gene seem to contribute to insulin resistance increasing the transcription rate of TNF-α. The TNF-α −863A allele is associated with a lower expression of TNF-α gene and less secretion of the cytokine. To investigate whether an abnormal TNF-α system regulation may contribute to early impairment of insulin action in first-degree relatives of patients with type 2 diabetes mellitus (DM), we studied the TNF-α -863C/A polymorphism and the soluble fraction of TNF-α receptor-2 (sTNFR2) concentration in these subjects in comparison to a control group. A total of 52% of subjects in the relatives’ group showed an abnormal oral glucose tolerance (either as impaired glucose tolerance [IGT] or diabetes) and had more features of the insulin resistance syndrome, despite showing similar body composition as controls. The plasma concentration of the sTNFR2 was higher and insulin sensitivity (%S) was lower in the relatives’ group than in the controls. Likewise, the TNF-α −863A allele was more commonly detected in the control group (10 of 41) than in the relative’s group (2 of 36, P = .029). In a multivariate linear regression analysis, neither TNF-α −863A allele nor sTNFR2 independently determined %S. Only body mass index (BMI) and the presence of a positive family history of DM were independent determinants of insulin resistance. In summary, our study showed a lower rate of TNF-α −863A allele and higher concentrations of sTNFR2 in first-degree relatives of DM subjects. These findings could be included among the genetic, metabolic, and clinical heterogeneity that characterizes the pathophysiology of DM. The presence of abnormalities in the TNF-α pathway could predispose to the development of DM in subjects at risk for the disease.
Metabolism: clinical and experimental 01/2003; 52(8):1068-1071. · 2.59 Impact Factor
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ABSTRACT: Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant chemokine CXCL10, also termed Interferon (IFN)-gamma -inducible protein (IP)-10 is pathogenetically involved in several immunoinflammatory and autoimmune diseases.
IFN-gamma and IP-10 were quantified by solid-phase ELISA in sera of patients with either newly diagnosed or long-term Type I (insulin-dependent) diabetes mellitus, and in sera of their healthy first degree relatives. The latter were subdivided into "low" and "high" risk prediabetic subjects depending on whether they were negative or positive for the anti-beta-cell autoantibodies ICA and GAD.
Compared with healthy control subjects (18%, 9/50), those with a low risk of disease (21%, 5/24) and the group of patients with long-term Type I diabetes (24%, 12/50), IP-10 was found more frequently and at increased concentrations in both newly diagnosed Type I diabetic patients (84%, 42/50) and in those with a high risk of disease (73%, 16/22); in the latter, the IP-10 concentrations correlated with those of IFN-gamma.
Circulating IP-10 concentrations is increased in patients with Type I diabetes, but only during the early and subclinical stage of the disease.
Diabetologia 09/2002; 45(8):1107-10. · 6.81 Impact Factor
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ABSTRACT: High uric acid concentration is a common finding in subjects with risk factors for cardiovascular disease (CVD), including some characteristics of the metabolic syndrome. However, its exact role in this setting and in the progression to type 2 diabetes mellitus (DM) is not well understood and could be affected by confounding factors such as hypertriglyceridemia. Our study aimed to establish the relationship between uric acid (avoiding the interference of high triglyceride levels), insulin sensitivity, and components of the metabolic syndrome in a group of subjects at high risk of developing DM. Among 201 subjects included in the study, 111 (55.2%) showed an abnormal oral glucose tolerance and uric acid levels higher than those measured in subjects with normal glucose tolerance. Body mass index (BMI), triglycerides, diastolic blood pressure (DBP), and 2-hour glycemia in the oral glucose tolerance test (OGTT) contributed independently to uric acid concentration (R2 =.59). However, uric acid did not affect either insulin sensitivity or glucose tolerance. The recovery tests revealed that a triglyceride concentration > or = 3 mmol/L interfered with the measurement of uric acid level when a colorimetric method was used, but not when a dry-chemistry method was used. In conclusion, uric acid concentration is higher in subjects at high risk of DM with abnormal glucose tolerance and is independently determined by various components of the metabolic syndrome.
Metabolism 03/2002; 51(3):372-5. · 2.66 Impact Factor
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ABSTRACT: Interferon-alpha (IFN-alpha) is now widely used in the treatment of chronic hepatitis C. Few patients have been reported as developing impaired glucose tolerance or diabetes mellitus (DM) using this therapy. The explanation for the development of DM in chronic hepatitis C treated with IFN-alpha is unclear. We report two patients who developed an abrupt onset of diabetes during IFN-alpha for chronic hepatitis C.
Two male middle-aged patients were admitted to our hospital for an abrupt onset of diabetes, in diabetic ketoacidosis, with a very short duration of hyperglycaemic symptoms. Their clinical course was similar. Case 1 never demonstrated any markers of pancreatic immunogenicity. Case 2 had high levels of decarboxylase glutamic acid autoantibodies (GADAb), before the IFN-alpha treatment that persisted. We compared initial beta-cell function and metabolic control with a group of middle-aged patients from our hospital who had recently been diagnosed with Type 1 diabetes mellitus (DM1). In contrast to these, the onset of the disease was particularly severe with beta-cell function substantially impaired and displaying unstable short-term metabolic control.
Type 1 diabetes should be considered as a potential complication if IFN is administered to patients with chronic hepatitis C. Its onset may be severe and result in short-term difficulties in metabolic control.
Diabetic Medicine 10/2001; 18(9):764-7. · 2.90 Impact Factor
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ABSTRACT: To test the effects of multifunctional protein 14 (MFP14), which shares structural homology with heat shock proteins (HSPs), on the development of Type I (insulin-dependent) diabetes mellitus in NOD mice.
MFP14 was given to euglycaemic female NOD mice from either the 4th to the 25th or from the 12th until the 35th week, or commencing one day before islet transplantation and until the reappearance of hyperglycaemia. Pancreata from NOD mice treated with multifunctional protein 14 for 14 consecutive weeks until 18 weeks of age were examined histologically for insulitis. Anti-CD3 and/or lipopolysaccharide (LPS)-induced blood levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-10, IL-12 and tumour necrosis factor (TNF)-alpha were measured by ELISA in 10 week-old female NOD mice treated for 6 consecutive weeks with either MFP14 or PBS. Unless otherwise stated, multifunctional protein 14 was administered daily 5 times a week at a dose of 25 microg. Control mice received PBS or, in selected experiments, heat-inactivated MFP14.
MFP 14 treated mice had a significantly lower incidence of spontaneous diabetes compared to control mice. The MFP14 was equally effective both upon early and late prophylaxis and the protection persisted until week 50 in mice treated from weeks 4 to 25. Insulitis was significantly reduced by the MFP14. The MFP14 also delayed recurrence of hyperglycaemia in syngeneic islet-transplanted NOD mice. Although MFP14 reduced anti-CD3 and/or LPS-induced blood levels of IFN-gamma, TNF-alpha and IL-12 it increased IL-4 and IL-10.
The MFP14 could be a possible candidate for the prevention or early treatment of human Type I (insulin-dependent) diabetes mellitus.
Diabetologia 08/2001; 44(7):839-47. · 6.81 Impact Factor
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ABSTRACT: Oral glucose tolerance test was evaluated, as well as, insulin sensitivity/secretion in a group of subjects at risk for type 2 diabetes mellitus.
Metabolic profile of subjects included in the new category, impaired fasting glucose (IFG), was also evaluated.
IFG and impaired glucose tolerance identify different alterations in glucose homeostasis.
Those subjects with IFG are heterogeneous in their oral glucose tolerance. They display defects not only in insulin sensitivity but also in their capacity to compensate for it.
Medicina Clínica 05/2001; 116(13):491-2. · 1.38 Impact Factor
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ABSTRACT: Interleukin (IL)-18 is a cytokine primarily produced by macrophages and capable of inducing T lymphocyte synthesis of interferon (IFN)-gamma. An up-regulated synthesis of IFN-gamma with consequential Type I cytokine dominance has been repeatedly shown in Type I (insulin-dependent) diabetes mellitus and thought to be involved in its pathogenesis. Because increased production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18, we compared the circulating levels of IL-18 in patients with newly diagnosed Type I diabetes with those of non-diabetic first-degree relatives and healthy control subjects.
Serum samples were obtained from healthy control subjects, patients with newly diagnosed Type I diabetes, and their healthy first-degree relatives. The latter were subdivided into "low" and "high" risk prediabetics depending on whether they were negative or positive for two or more of the anti-pancreatic autoantibodies ICA, GAD, IA-2 and IAA. Serum levels of IL-18 were measured by solid-phase ELISA.
Interleukin (IL)-18 was above the detection limit of 25 pg/ml in 7 of 40 (17%) healthy control subjects, in 5 of 35 (14%) patients and in 3 of 30 (10%) first-degree relatives at low risk of developing Type I diabetes. In contrast, IL-18 could be detected in 19 of 28 (68%; p < 0.0001) relatives at high risk. The mean serum level of IL-18 was higher in these individuals when compared with the low-risk relatives, patients and control subjects.
IL-18 serum levels are increased selectively during the early, subclinical stage of Type I diabetes.
Diabetologia 04/2001; 44(3):309-11. · 6.81 Impact Factor
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E Martinez,
A Mocroft,
M A García-Viejo,
J B Pérez-Cuevas,
J L Blanco,
J Mallolas,
L Bianchi, I Conget,
J Blanch,
A Phillips,
J M Gatell
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ABSTRACT: Risk factors for lipodystrophy in patients infected with HIV-1 treated with highly active antiretroviral therapy (HAART) containing HIV-1 protease inhibitors are poorly understood. We aimed to identify the risk factors for lipodystrophy in antiretroviral-naive HIV-1-infected adults on HAART.
Moderate or severe body-fat changes were clinically assessed and categorised as subcutaneous lipoatrophy, central obesity, or both, in all consecutive antiretroviral-naïve HIV-1-infected adults who began HAART with two nucleoside reverse transcriptase inhibitors plus at least one protease inhibitor from October, 1996, to September, 1999. A person-years analysis was used to calculate the incidence of types of lipodystrophy, and Cox proportional hazards models were used to describe the univariate and multivariate factors associated with progression to any lipodystrophy.
After a median follow-up of 18 months, 85 (17%) of the 494 patients developed some type of lipodystrophy. The incidences of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and lipodystrophy with central obesity were 11.7 (95% CI 9.2-14.2), 9.2 (7.0-11.4), and 7.7 (5.7-9.7) per 100 patient-years. An increased risk for any lipodystrophy was found among women as compared with men (relative hazard 1.87 [1.07-3.28]), heterosexuals (2.86 [1.50-5.48]), and homosexuals (2.17 [1.07-4.42]) as compared with intravenous drug users, with increasing age (1.33 per 10 years older [1.08-1.62]), and with the duration of exposure to antiretroviral therapy (1.57 per 6 months extra [1.30-1.88]) but not with any individual antiretroviral agent. The factors associated with an increased risk for lipodystrophy with subcutaneous lipoatrophy or lipodystrophy with central obesity were very similar to those associated with any lipodystrophy. The duration of indinavir use may represent an additional contribution for the development of lipodystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.064).
Risk factors associated with development of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and tipodystrophy with central obesity in patients infected with HIV-1 who were receiving HAART containing protease inhibitors are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to an particular antiretroviral agent.
The Lancet 03/2001; 357(9256):592-8. · 38.28 Impact Factor
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Diabetes Care 01/2001; 23(12):1864-6. · 8.09 Impact Factor
