Peripheral, rather than hepatic, insulin resistance and atherogenic lipoprotein phenotype predict cardiovascular complications in NIDDM

Abstract Microalbuminuria, hypertension and hyper-insulinaemia are three independent risk factors for cardiac disease in non insulin-dependent diabetes (NIDDM). However, it is unknown to what extent hyperinsulinaemia reflects resistance to insulin action at hepatic, extrahepatic or at both sites. A cross-sectional study from our Department showed that peripheral insulin resistance, hypertension, microalbuminuria and lipid abnormalities are associated in NIDDM. Non diabetic individuals with the so-called ‘atherogenic lipoprotein phenotype’, characterized by small dense low density lipoproteins (LDL subclass pattern B) have up to 3-fold higher risk of myocardial infarction. The aim of the present study was to investigate whether impaired peripheral insulin sensitivity, during euglycaemic-hyperinsulinaemic clamp, as well as abnormalities in lipid concentrations and LDL size, predict abnormalities in albumin excretion rate, blood pressure and cardiac function in 73 consecutive normotensive (<85 mmHg diastolic level) and nor-moalbuminuric (<15 μg min^-1 daily albumin excretion rate) NIDDM patients. These patients showed a bimodal distribution of whole body glucose utilization rate, a parameter of peripheral insulin sensitivity. The cut-off point between the two modes of distribution was located close to the mean value minus one standard deviation in a population of 24 control subjects. Therefore, this latter value was used to identify two subgroups inside the overall population of NIDDM patients, i.e. 28 patients (group 1), with whole body glucose utilization rate, above, and 45 patients (group 2), below, the mean value minus 1 SD in the 24 controls. Both groups 1 and 2 had impaired insulin sensitivity at hepatic site, as assessed by the degree of inhibition of hepatic glucose output during insulin administration (controls vs. group 1 vs. group 2: 925±235 vs. 952±166 vs. 506±121; P>0·001). The two groups displayed similar patterns of age, gender, body weight, diabetes duration, HbA_1c and cardiac ischaemic events. During 6-year follow-up the rate of occurrence of microalbuminuria (>20 μg min^-1) (7% vs. 15%, P<0·01) and diastolic hypertension (>90 mmHg) (14 vs. 30%, P<0·05) was significantly higher in group 2 than in group 1 NIDDM patients. Events of cardiac ischaemic disease were more frequently found among group 2 rather than group 1 patients, during the follow-up (angina pectoris: 3/28 subjects in group 1 vs. 9/45 subjects in group 2, P<0·05; positive resting ECG: 3/28 subjects in group 1 vs. 9/45 subjects in group 2; positive exercise ECG 4/28 in group 1 vs. 11/45 in group 2). Group 2 patients were also characterized by higher triglyceride and lower high density lipoprotein cholesterol levels and by LDL subclass pattern B. Peripheral, rather than hepatic, resistance and atherogenic lipoprotein phenotype are the clinical hallmark of NIDDM patients who are prone to develop microalbuminuria, hypertension and cardiac ischaemic disease.     

LONG-LASTING LOWERING OF SERUM GROWTH HORMONE AND PROLACTIN LEVELS BY SINGLE AND REPETITIVE CABERGOLINE ADMINISTRATION IN DOPAMINE-RESPONSIVE ACROMEGALIC PATIENTS

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition.     

Gallium-67-citrate Scanning in Tuberculous Peritonitis

A 32-year old black, alcoholic male was noted to have an abnormal Gallium-67-citrate scan during a work-up for persistent fever. Surgical biopsies revealed findings of the dry form of tuberculosis peritonitis. The literature concerning Gallium-67-citrate scanning was reviewed and its usefulness in inflammatory disease states (including two reports of positive scans in tuberculous peritonitis) was demonstrated. In addition, we have considered the possible mechanisms of Gallium-67-citrate uptake by inflammatory cells and its probable relationship to the granulomas associated with tuberculous peritonitis. We conclude that Gallium-67-citrate scanning is an important diagnostic procedure in the evaluation of a fever of unknown origin. Moreover, it may significantly shorten the diagnostic work-up of those cases of tuberculous peritonitis.     

Five-Year Safety and Efficacy of a Novel Polymethylmethacrylate Aesthetic Soft Tissue Filler for the Correction of Nasolabial Folds

BACKGROUND A novel soft tissue filler composed of polymethylmethacrylate (PMMA) microspheres suspended in a collagen gel matrix containing 0.3% lidocaine (ArteFill, Artes Medical, Inc.) was recently approved by the Food and Drug Administration for the correction of nasolabial folds. A randomized, multicenter, controlled pivotal trial performed in the United States established the safety and efficacy of this medical device throughout a 12-month study period.
OBJECTIVE The objective was to substantiate the long-term 5-year safety and efficacy of this novel soft tissue PMMA filler.
METHODS AND MATERIALS Attempts were made to contact all subjects treated with the PMMA filler that were enrolled in the original pivotal study. Safety was assessed by standard adverse event reporting methods. Efficacy was determined using a validated six-point facial fold assessment photometric grading scale using blinded observers' assessment of standardized photographs.
RESULTS Subjects ( n =119) demonstrated significant improvement in nasolabial folds comparing baseline (before any treatment) to 5 years after their last treatment ( p <.001). Notably, subjects also demonstrated continued improvement between 6 months after their last treatment and Year 5 ( p =.002). No serious unanticipated device-related adverse events were reported.
CONCLUSION This PMMA filler is the first soft tissue filler to demonstrate continued improvement and persistence of correction over a 5-year period posttreatment.