Improvement of psoriasis during glucagon-like peptide-1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T-cell number: a prospective case-series study.

BACKGROUND: A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear. OBJECTIVES: To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment. METHODS: Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites. RESULTS: The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions. CONCLUSIONS: The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.

Advances in cystic fibrosis-related diabetes: Current status and future directions.

AIMS: The aim of this review is to give an update of the recent advances in the pathophysiology, prognosis, diagnosis and treatments of cystic fibrosis-related diabetes (CFRD). METHODS: The literature survey focuses on original and review articles dealing with CFRD between 2006 and 2023, and in particular with: pathophysiology, risk and predictive factors, screening, chronic complications of CFRD, management and the effects of CFTR channel modulator therapies on glucose homeostasis, using PubMed®. RESULTS: The rising prevalence of CFRD is due to prolonged life survival among patients with cystic fibrosis (CF). Advances in the understanding of the pathophysiology highlight the singularity of CFRD. Adherence to diagnostic guidelines remains challenging. Besides the classical OGTT, alternative diagnostic tests are being considered: HbA1c measurement, continuous glucose monitoring (CGM), intermediate measurements of alternative glucose tolerance stages through OGTT and homeostatic model assessment (HOMA). Early treatment of (pre)diabetes in CF patients is mandatory. The advent of CFTR channel modulator therapies have created a paradigm shift in the management of CF: they seem to improve glucose homeostasis, but the mechanism remains unclear. CONCLUSION: CFRD management is an ongoing concern. Optimal care has reduced the negative impact of CFRD on lung function, nutrition, and survival. Increasing prevalence of CFRD and prolonged lifespan lead to more microvascular complications. New screening tools (Hba1c, CGM, HOMA) show potential for better classification of patients. The effect of CFTR modulators on glucose metabolism warrants further research.

[Knowledge of the general population about hypertension and diabetes mellitus in South Kivu, Democratic Republic of Congo]. / Connaissances de la population générale sur l'hypertension artérielle et le diabète sucré au Sud-Kivu, République démocratique du Congo.

BACKGROUND: In the Democratic Republic of Congo (DRC), a country in a post-conflict period, high priority cannot be given to non-communicable diseases other than to emergencies. This certainly involves inadequacy in raising awareness for prevention of these diseases. OBJECTIVE: To evaluate the level of knowledge of the Congolese general population on hypertension and diabetes mellitus. METHODS: Responses to a questionnaire from 3% of the general population aged 15 and older in the city of Bukavu and two rural areas: Hombo and Walungu (South Kivu, eastern DRC), recruited after stratification by ward in the city of Bukavu and a group of prone villages were expected. The questions focused on identification, testing, causes, complications and treatment of hypertension and diabetes mellitus. RESULTS: Of the 7770 respondents, screening for hypertension and diabetes mellitus affected only 14.9% and 7.3% of subjects respectively. Knowledge of these two conditions was generally low in the general population, although better in the subgroups of patients and those with higher socioeconomic level (P<0.05). Use of the medias was also associated with better knowledge (P<0.05). CONCLUSIONS: This study shows that knowledge about hypertension and diabetes mellitus and their testing in South Kivu is low. It is imperative that the Congolese government includes non-communicable diseases in its priorities of the millennium. Similarly, the WHO should actively contribute to screening for them in low-income countries.

1-h post-load plasma glucose for detecting early stages of prediabetes.

Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 min during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria. The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of "prediabetes" before prediabetes evolves as conventionally defined.

Current status of insulin degludec in type 1 and type 2 diabetes based on randomized and observational trials.

Insulin degludec is a new ultra-long-action basal insulin. Using treat-to-target protocols, controlled trials have shown comparable HbA1c reductions with insulin degludec and comparators in both type 1 and type 2 diabetes. Most studies identify, however, better control of fasting plasma glucose with insulin degludec vs. either insulin glargine U100 or detemir, and all have consistently demonstrated clinically relevant decreases in (nocturnal) hypoglycaemic episodes. These characteristics have provided added therapeutic value for insulin degludec in clinical practice. Thus, the aim of this review is to discuss, within the context of randomized and observational studies, the clinical effects of insulin degludec use in type 1 and type 2 diabetes.

Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.

We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.

Long-term effects of GLP-1 receptor agonists in type 2 diabetic patients: A retrospective real-life study in 131 patients.

AIM: We evaluate retrospectively long-term effects of GLP-1 receptor agonists in type 2 diabetic patients treated between 2008 and 2016. METHODS: 131 patients treated by GLP-1 receptor agonists (GLP-1RAs) were included. The objective was to evaluate the evolution of glycated hemoglobin (HbA1c) during a period up to 4 years. The secondary objectives consisted of analysing the long-term effects of treatment on body mass index (BMI), blood pressure and lipids; reporting the proportion of patients who reached HbA1c objectives; estimating the time before treatment failure and determining predictive factors of failure. We also compared twice-daily exenatide to once-daily liraglutide on the major parameters. RESULTS: HbA1c improved significantly, mostly during the first year of treatment (-1.2%), and this effect was maintained after 4 years (-1.4% vs. baseline). At 1 year, 26% and 47% of subjects achieved HbA1c levels <7.0% and 7.5%, respectively. Treatment failure was observed in 51% of patients after a mean duration of GLP-1RA treatment of 50 months. Half of patients had failed after 42 months. Baseline HbA1c greater than 9.0% and male gender were predictive factors of treatment failure. BMI also decreased: -0.9 kg/m2 the first year, -1.9 kg/m2 after 4 years. No significant difference was found between patients treated with exenatide and liragutide over time. CONCLUSIONS: The beneficial effects of GLP-1RAs on HbA1c reached a plateau after the first year of treatment and are maintained at 4 years only in one third of patients. Failure occurred predominantly in men with a baseline HbA1c greater than 9%.

Coronary in-stent restenosis in diabetic patients after implantation of sirolimus or paclitaxel drug-eluting coronary stents.

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no difference in the rate of restenosis with sirolimus-(n=8) compared with paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.

Insulin sensitivity, adjusted beta-cell function and adiponectinaemia among lean drug-naive schizophrenic patients treated with atypical antipsychotic drugs: a nine-month prospective study.

Atypical antipsychotic drugs (AADs) induce weight gain and truncal adiposity, and even the metabolic syndrome (MetS), which may progress to IFG/IGT or DM. AAD effects in lean schizophrenic patients without MetS have not been documented, especially in terms of weight gain and changes in insulin sensitivity (S), beta-cell function (beta) and adiponectinaemia. We prospectively determined the effects of nine-month therapy with AADs on anthropometrics, metabolism and adiponectinaemia, including homoeostasis model assessment (HOMA) modelling of S, beta and betaxS (hyperbolic product, assessing individual beta adjusted for S). We analyzed 36 schizophrenic subjects (M/F: 24/12; Caucasian: n=23, North African: n=12, South Asian: n=1) aged 35+/- years (mean+/-one S.D.) free of MetS (NCEP-ATPIII), of whom 19 study completers were evaluated following AAD treatment. S, beta, betaxS and adiponectin were measured at zero, three and nine months. At nine months, BMI had risen from 22+/-2 to 25+/-2kg/m(2) (P<0.001) and waist circumference from 85+/-8 to 91+/-11cm (P<0.001), while adiponectin decreased from 10.4+/-5.1 to 7.4+/-3.8mug/mL (P<0.001). Blood pressure and lipids were unaffected. S decreased from 138+/-49 to 110+/-58% (P=0.006) and beta increased from 83+/-24 to 100+/-40% (P=0.034). As a result, betaxS decreased from 106+/-19 to 91+/-27% (P=0.015). Fasting glycaemia rose from 89+/-5 to 96+/-9mg/dL (P=0.007). On study completion, 21% had IFG. Long-term use of AADs in lean, drug-naive, schizophrenics initially free of MetS induced weight gain and truncal fat accumulation associated with decreases in adiponectin and hyperbolic product, explaining the increased fasting glycaemia and impaired fasting glucose seen in predisposed individuals.

The role of alexithymia factors in glucose control of persons with type 1 diabetes: a pilot study.

OBJECTIVE: To clarify the respective contribution of demographic characteristics, health conditions and three psychological variables (depression, anxiety, alexithymia) for glycaemic control measured by glycated hemoglobin (HbA1c). MATERIALS AND METHODS: Sixty-four persons diagnosed with type 1 diabetes completed psychological measures and demographic information at admission (T1) to the hospital and in a follow-up (+8 weeks) (T2). Additional information about their health conditions was also considered. RESULTS: At T1, the alexithymia factor "difficulties describing feelings" (DDF) predicted HbA1c over and above the predictive power of demographic information, health conditions, anxiety, and depression. Additionally, higher decrease in HbA1c from T1 to T2 was predicted by higher scores on the alexithymia factor DDF at admission over and above the other predictors. CONCLUSION: DDF is an important predictor of glucose control. Scoring higher on this factor is related to poorer glycaemic control at admission. Additionally, people with higher scores on this factor seem to benefit highly from the treatment administered at the hospital.

Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites.

BACKGROUND: Part of the fructosamines that are bound to intracellular proteins are repaired by fructosamine 3-kinase (FN3K). Because subject-to-subject variations in erythrocyte FN3K activity could affect the level of glycated haemoglobin independently of differences in blood glucose level, we explored if such variability existed, if it was genetically determined by the FN3K locus on 17q25 and if the FN3K activity correlated inversely with the level of glycated haemoglobin. RESULTS: The mean erythrocyte FN3K activity did not differ between normoglycaemic subjects (n = 26) and type 1 diabetic patients (n = 31), but there was a wide interindividual variability in both groups (from about 1 to 4 mU/g haemoglobin). This variability was stable with time and associated (P < 0.0001) with two single nucleotide polymorphisms in the promoter region and exon 6 of the FN3K gene. There was no significant correlation between FN3K activity and the levels of HbA1c, total glycated haemoglobin (GHb) and haemoglobin fructoselysine residues, either in the normoglycaemic or diabetic group. However, detailed analysis of the glycation level at various sites in haemoglobin indicated that the glycation level of Lys-B-144 was about twice as high in normoglycaemic subjects with the lowest FN3K activities as compared to those with the highest FN3K activities. CONCLUSION: Interindividual variability of FN3K activity is substantial and impacts on the glycation level at specific sites of haemoglobin, but does not detectably affect the level of HbA1c or GHb. As FN3K opposes one of the chemical effects of hyperglycaemia, it would be of interest to test whether hypoactivity of this enzyme favours the development of diabetic complications.

Bone density and markers of bone remodeling in type 1 male diabetic patients.

AIMS: To assess the prevalence and severity of bone disease in type 1 diabetic patients and to determine serum markers of bone remodeling as well as their relationship with bone mineral density (BMD). METHODS: BMD [by dual energy x-ray absorptiometry (DXA)] and serum markers of bone remodeling [osteocalcin, c-terminal telopeptide of type I collagen (CTX)], leptin and osteoprotegerin (OPG) were measured in 42 adult males with type 1 diabetes. Twenty-four non-diabetic subjects served as controls. RESULTS: In 40% of the patients, osteopenia at the lumbar spine (L1-L4) and/or at the left hip was found, and 7% met criteria for osteoporosis. L1-L4 BMD z-score was correlated with age (r=0.365, P=0.018) and a similar trend was observed at left hip. L1-L4 BMD z-score was negatively correlated with CTX and osteocalcin (r=-0.343, P=0.028; r=-0.376, P=0.024, respectively). A significant correlation was evidenced between BMD z-score at both lumbar spine and left hip and leptin values (r=0.343, P=0.03; r=0.395, P=0.012, respectively) but after adjustment for weight this correlation was no longer significant. Osteocalcin, CTX and leptin concentrations were comparable between patients and controls, while OPG concentrations tend to be higher in diabetic subjects (P=0.08). CTX was negatively correlated with age (r=-0.390, P=0.012) and positively correlated with osteocalcin (r=0.696, P<0.001). OPG was positively correlated with age (r=0.507, P=0.001). CONCLUSION: Our results suggest that in diabetic subjects osteopenia is a relatively frequent complication but bone loss is attenuated with age progression. Whether this is also mediated by OPG and/or leptin remains to be confirmed.

Gastric acid and pancreatic polypeptide responses to sham feeding are impaired in diabetic subjects with autonomic neuropathy.

To assess the relationship between cardiac and extra-cardiac dysfunction in diabetic autonomic neuropathy, the gastric acid output and the pancreatic polypeptide (hPP) secretion in response to sham feeding were evaluated in diabetic patients with (group 1) and without (group 2) cardiac autonomic neuropathy (CAN), and in normal subjects (group 3). All patients assigned to the group with CAN exhibited an impaired beat-to-beat heart rate variation during deep breathing. The basal gastric acid output was comparable in the three groups (1.3 +/- 0.5, 2.8 +/- 1.5, and 3.9 +/- 1.5 mmol/h, respectively). In contrast, the gastric acid output stimulated by sham feeding was significantly lower in patients with CAN (5.3 +/- 1.3 mmol/h) than in diabetic subjects without CAN (14.0 +/- 3.5 mmol/h; P less than 0.01) and in controls (10.9 +/- 3.1; P less than 0.05). The maximal gastric acid secretion capacity, determined after pentagastrin injection, was similar in all patients. Mean basal hPP concentrations were comparable in the three groups (185 +/- 53 pg/ml, 131 +/- 29 pg/ml, and 116 +/- 19 pg/ml). In the controls and diabetic subjects without CAN, a significant mean 60% increase of the hPP levels above basal values was observed during sham feeding. In contrast, no significant hPP response occurred in the group with CAN. These data suggest that diabetic CAN is associated with dysfunctions of the vagal pathways controlling the gastric acid output and the hPP secretion. Moreover, the results demonstrate a strong association between cardiac autonomic neuropathy and gastric vagal neuropathy (P less than 0.001).

Pancreas transplantation for treatment of generalized allergy to human insulin in type 1 diabetes.

We report the case of a 29-year-old man with a 14-year history of type 1 diabetes, normal renal function, and mild diabetic retinopathy. The patient progressively developed a generalized allergic reaction to two insulin excipients--protamine and metacresol--with systemic manifestations of tremor, tachycardia, vertigo, shortness of breath, and short episodes of unconsciousness causing him to be out of work. In June 2003, he received a vascularized cadaveric pancreas transplant using induction with polyclonal antibodies along with tacrolimus and sirolimus but without steroids. A hyperglycemic episode following corticosteroid therapy for rejection treatment required reintroduction of insulin therapy with prompt reappearance of allergic manifestations. Now, the patient is euglycemic without insulin or allergic manifestations and a glycated hemoglobin of 6.4%.

Use of an artificial pancreas as a tool to determine subcutaneous insulin doses in juvenile diabetes.

The present study was undertaken to examine the feasibility of determining the most appropriate subcutaneous insulin treatment in unstable diabetes on the basis of the circadian hormonal profile delivered by an artificial pancreas. The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas. The usual insulin treatment was continued to that day. Examination of the insulin pattern revealed by the artificial pancreas suggested that a valid scheme for subsequent treatment should consist of two daily injections of a mixture of short-acting and intermediate-acting insulins, which was administered to the patients beginning with the injection given after the artificial pancreas onwards. The new insulin regimen was characterized by a total daily dose that increased from 0.93 +/- 0.10 to 1.20 +/- 0.10 U/kg body weight (mean +/- SEM; P less than 0.005) as well as by a higher proportion of the dose given as regular insulin (37.1 +/- 6.9% before vs. 56.0 +/- 2.1% after; P less than 0.05). These changes led to a better control of blood glucose in 10 patients, as evidenced by a decrease of both the M value and the mean of all blood glucose levels. The mean MAGE index was not decreased, however, by the new insulin program, thereby suggesting that the lability of the disease remained unabated. These results indicate that subcutaneous treatment consisting of two daily injections of regular and intermediate-acting insulins and comprising 50 to 60% of the former could improve the metabolic control in unstable diabetes. The artifical pancreas provided a rapid and simple means to determine the appropriate doses for each type of insulin.

Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.

OBJECTIVE: The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance. RESEARCH DESIGN AND METHODS: Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA). RESULTS: We found that 31% of the cohort (group 1) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 micromol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 micromol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively The degree of insulin resistance was similar in groups 1 and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta-cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016). CONCLUSIONS: Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.

Comparison of plasma glucose and plasma free insulin during CSII and intensified conventional insulin therapy.

The plasma glucose and plasma free insulin profiles of six totally insulin-dependent diabetic patients were compared during periods of 4 days in hospital under a conventional insulin therapy (ICIT) comprising 4 daily injections of regular insulin and under continuous subcutaneous insulin infusion (CSII). Two profiles of prandial insulin administration with CSII were compared: a rectangular (R) and an exponential wave (E) in which 50% of the dose was given rapidly followed by an exponential decrease. In both cases, the basal infusion rate was increased by 30-50% between 5 a.m. and 8 a.m. Mean circadian blood glucose was equally good with ICIT: R and E: 7.0 +/- 0.9, 7.3 +/- 1.0, and 7.1 +/- 1.0 mmol/L, respectively. In five patients, fasting plasma glucose was higher with ICIT than with R and E (12.7 +/- 1.8 versus 6.9 +/- 1.0 and 6.8 +/- 0.8 mmol/L, respectively; t test: P less than 0.05; Wilcoxon: P = 0.06). Mean plasma free insulin level was significantly higher (t test: P less than 0.005; Wilcoxon: P less than 0.05) with ICIT (0.46 +/- 0.04 nmol/L) than with R (0.37 +/- 0.04 nmol/L) or E (0.36 +/- 0.05 nmol/L), although the daily doses were similar. In conclusion, CSII leads to a better glycemic control than ICIT, since it appears to prevent the morning rise of blood glucose.

Hemostasis variables in type I diabetic patients without demonstrable vascular complications.

OBJECTIVE: To determine hemostasis variables in type I diabetic patients without clinically demonstrable micro- and macroangiopathy and to relate them to glycemic control. RESEARCH DESIGN AND METHODS: Fifty patients and 50 comparable control subjects were enrolled in this study. The patients were subdivided in two groups, according to their level of HbA1c (group 1, n = 30, HbA1c < or = 8%; group 2, n = 20, HbA1c > 8%). We determined the platelet count, the platelet aggregation in the spontaneous state and in the presence of ADP or collagen, beta-thromboglobulin, platelet factor 4, fibrinogen, von Willebrand factor (factors VIII:C, VIIIR:Ag, and VIIIR:VW), plasma and urinary fibrinopeptide A, euglobulin lysis time, anticoagulant proteins C and S, and plasma viscosity. RESULTS: All coagulation variables were significantly higher in diabetic patients compared with control subjects. Moreover, when the patients were subdivided according to their levels of HbA1c, the hemostatic disturbances appeared significantly more pronounced in the poorly controlled than in the well-controlled subjects. CONCLUSIONS: This study confirms the existence of a state of hypercoagulability in type I diabetes. This hypercoagulability may be related to poor glycemic control. Our study suggests that the hemostasis disturbances precede demonstrable vascular complications.

Serum lipoprotein(a) in patients with diabetes mellitus.

OBJECTIVE: To investigate subjects with different types of diabetes mellitus regarding their serum levels of lipoprotein(a). High serum Lp(a) concentration is associated with a high risk of coronary heart disease. Diabetic patients are prone to developing coronary heart disease. RESEARCH DESIGN AND METHODS: The subjects were 66 type I diabetic patients, 100 type II diabetic patients treated with diet alone or diet combined with oral hypoglycemic agents, and 46 insulin-requiring type II diabetic patients. Subjects were compared with 142 nondiabetic outpatients. RESULTS: Subjects with insulin-requiring type II diabetes mellitus were found to have an increase both in serum Lp(a) concentration and in prevalence of serum Lp(a) concentration > 30 mg/dl compared with the other groups of diabetic patients and nondiabetic control subjects. A nonsignificant increase in the prevalence of coronary heart disease was also found in insulin-requiring type II diabetic patients. The levels of serum concentrations of Lp(a) were not significantly related to the degree of glycemic control, duration of diabetes, presence of macrovascular disease, or intake of female hormone therapy. High levels of Lp(a) in this group of diabetic patients could not be explained by the presence of albuminuria. CONCLUSIONS: Insulin-requiring type II diabetic patients have high levels of Lp(a). Chronic hyperinsulinemia might be an eventual causal factor.

Exercise and posture-related changes of atrial natriuretic factor and cardiac function in diabetes.

To study whether the release of atrial natriuretic factor (ANF) was altered in diabetic cardiac autonomic neuropathy (CAN), we determined plasma ANF concentrations during exercise and changes of posture in three groups of age- and sex-matched subjects (9 healthy subjects, 7 diabetic patients with CAN, and 7 diabetic patients without CAN). During exercise, plasma ANF concentrations rose threefold (P less than .001), and this increase was similar in the three groups. However, heart-rate response to exercise was impaired in the two groups of diabetic patients (P less than .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P less than .03 vs. patients without CAN). In healthy subjects and patients without CAN, the increases of ANF during exercise correlated significantly with those of heart rate, systolic blood pressure, and rate-pressure product (P less than .01). In patients with CAN, the correlation was found exclusively with heart rate (P less than .01). An increase of ventricular ejection fraction occurred in all groups (P less than .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P less than .002) was observed in all subjects, reflecting preserved sympathetic control of vessels. In conclusion, exercise induces an increase of plasma ANF in diabetic patients with CAN. This increase, occurring similarly to healthy subjects, indicates that autonomic activation plays a minor role in ANF release during exercise. Impaired heart-rate response to exercise in patients without CAN suggests early damage of autonomic function, undetected by conventional rest tests.