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Biomedical subjects

G Ghirlanda

Publications and source records attributed to G Ghirlanda.

At least 37 records · Page 2Linked to original sources
PubMed1999

Insulin-dependent diabetes mellitus affects eradication rate of Helicobacter pylori infection.

BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. METHODS: Thirty-one patients (18 male, 13 female, 39+/-12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37+/-10 years) were evaluated. H. pylori infection was assessed through 13C-urea breath test. A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg t.i.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. RESULTS: All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. CONCLUSIONS: IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.

Adult↗
PubMed1998

From synthetic coiled coils to functional proteins: automated design of a receptor for the calmodulin-binding domain of calcineurin.

A series of synthetic receptors capable of binding to the calmodulin-binding domain of calcineurin (CN393-414) was designed, synthesized and characterized. The design was accomplished by docking CN393-414 against a two-helix receptor, using an idealized three-stranded coiled coil as a starting geometry. The sequence of the receptor was chosen using a side-chain re-packing program, which employed a genetic algorithm to select potential binders from a total of 7.5x10(6) possible sequences. A total of 25 receptors were prepared, representing 13 sequences predicted by the algorithm as well as 12 related sequences that were not predicted. The receptors were characterized by CD spectroscopy, analytical ultracentrifugation, and binding assays. The receptors predicted by the algorithm bound CN393-414 with apparent dissociation constants ranging from 0.2 microM to >50 microM. Many of the receptors that were not predicted by the algorithm also bound to CN393-414. Methods to circumvent this problem and to improve the automated design of functional proteins are discussed.

Algorithms↗
PubMed1998

Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus.

BACKGROUND/AIM: Insulin-dependent diabetes mellitus (IDDM) is the result of an autoimmune destruction of pancreatic Langerhans beta cells. Helicobacter pylori infection, the most common cause of gastritis and peptic ulcer, has been associated with some autoimmune diseases. The aim of this study was to evaluate the prevalence of H. pylori infection and gastrointestinal (GI) symptoms in patients with IDDM. METHODS: 116 patients (50 males and 66 females, mean age: 35 +/- 11 years) affected by IDDM were evaluated; 50 healthy subjects matched for age and sex were utilized as a control group. H. pylori infection was determined by a [13C]urea breath test. IDDM duration, daily dosage of insulin and prevalence of GI symptoms (bloating, pyrosis, epigastric pain, belching, halitosis, nausea) were assessed. RESULTS: The prevalence of H. pylori infection was similar in IDDM patients and in controls (37 vs 34%, respectively). In both groups, the mean age was higher in infected subjects. The mean IDDM duration was significantly greater in infected patients (19 +/- 12 vs 13 +/- 10 years, P < 0.006). Prevalence of infection was directly related to the duration of IDDM (<1 year, 23%; 1-3 years, 32%; >3 years, 40%). The daily dosage of insulin did not differ between infected and non-infected subjects. H. pylori contaminated patients showed a significantly higher prevalence of bloating, pyrosis and epigastric pain when compared with non-infected subjects; conversely, prevalence of belching, halitosis and nausea did not differ between groups. CONCLUSION: The prevalence of H. pylori infection is high in patients affected by IDDM; however, it does not differ from the infection rate observed in a control group. The rate of infection increases with IDDM duration. Bloating, pyrosis and epigastric pain appear to define infection status better.

Adult↗
PubMed1998

Early renal involvement in diabetes mellitus: comparison of renal Doppler US and radioisotope evaluation of glomerular hyperfiltration.

PURPOSE: To evaluate the usefulness of Doppler ultrasonography (US) in the diagnosis of hyperfiltration in patients with insulin-dependent diabetes mellitus (IDDM). MATERIALS AND METHODS: Eighty-one consecutive patients with IDDM were studied. All patients were normotensive and had normal creatinine and blood urea nitrogen levels. The glomerular filtration rate (GFR) was evaluated by means of plasma clearance of chromium-51 ethylenediaminetetraacetic acid, urinary albumin excretion, US evaluation of renal volume, and Doppler evaluation of resistance index (RI) in the renal interlobar arteries. The patients were divided according to GFR into the following groups: those with hyperfiltering kidneys (group 1, n = 40) and those with normofiltering kidneys (group 2, n = 41). RESULTS: The median renal volume was 351 mL (95% CI = 337 mL, 379 mL) in group 1 and 318 mL (95% CI = 300 mL, 335 mL) in group 2 (P = .005). The number of patients with microalbuminuria was significantly lower in group 1 than in group 2 (P = .02). The median RI was significantly lower in group 1 (0.55; 95% CI = 0.53, 0.57) than in group 2 (0.57; 95% CI = 0.56, 0.59) (P = .04). An RI of less than 0.5, a renal volume greater than 410 mL/m2, and the absence of microalbuminuria were independent predictors of hyperfiltration. An RI of less than 0.5 and a renal volume greater than 410 mL/m2 showed high specificity (98% and 95%, respectively) and poor sensitivity (25% and 23%, respectively) in the diagnosis of hyperfiltration in IDDM patients. CONCLUSION: Both RI and renal volume showed correlation with GFR, but neither parameter is sufficiently sensitive in screening for hyperfiltration in IDDM patients.

Adult↗
PubMed1998

Distortion-product otoacoustic emissions and selective sensorineural loss in IDDM.

OBJECTIVE: To provide information about possible subclinical damage of the cochlear outer hair cells (OHCs) by means of transiently evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in subjects with IDDM. RESEARCH DESIGN AND METHODS: TEOAEs and DPOAEs were recorded in 47 IDDM patients with normal hearing and in age- and sex-matched nondiabetic subjects. Peripheral neuropathy was diagnosed by nerve conduction velocity (NCV) at the peroneal and surral nerves. RESULTS: A subclinical peripheral neuropathy was found in 15 diabetic patients. Mean TEOAE amplitude was found to be significantly reduced in diabetic patients with a reduced NCV (7.6 +/- 3.2 dB; Scheffé's test: P = 0.03), but not in those without neuropathy (9.5 +/- 4.3 dB), with respect to control subjects (11 +/- 3.1 dB). Neuropathic patients also showed mean reduced DPOAE amplitude values in the region of middle and high frequencies from 1,306 to 5,200 Hz (P < 0.05), whereas no difference was found at the lowest-frequency amplitudes. A frequency-selective reduction of DPOAEs was also found in non-neuropathic patients (P < 0.05) in the region of higher frequencies at 3,284, 4,126, and 5,200 Hz compared with control subjects. No correlations were found among duration of diabetes, HbA1c values, TEOAEs and DPOAEs. CONCLUSIONS: Our results suggest that IDDM patients show an early abnormality of the micromechanical properties of the OHCs. In IDDM patients without a subclinical peripheral neuropathy, damage is limited to the higher frequencies and can be detected only by DPOAEs, whereas in IDDM patients with neuropathy, damage also involves the middle range of frequencies and can be detected by TEOAEs and DPOAEs. Therefore, DPOAEs seem to be able to detect the earliest cochlear selective-frequency dysfunction in IDDM patients without peripheral neuropathy. DPOAEs appear to be of greater clinical interest than TEOAEs; the former seem to be frequency specific and can be recorded at any chosen frequency, including high frequencies.

Acoustic Stimulation↗
PubMed1998

Hyperfiltration in patients with type I diabetes mellitus: a prevalence study.

AIM: An increase in glomerular filtration rate (GFR) and renal plasma flow (EFPR) may be considered as prognostic factors for the progression of diabetic nephropathy; however the real predicting value of hyperfiltration in the development of incipient and overt nephropathy is as yet unknown. We have examined the prevalence of hyperfiltration in a population of normotensive adult IDDM patients and the possible effect of long-term metabolic control on glomerular hemodynamics. MATERIALS AND METHODS: We measured GFR and ERPF values in 177 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 30 healthy subjects by single bolus intravenous injection of 1 miroCu/kg [51Cr]-EDTA and 0.2 microCu/kg [125I]-Hippuran intravenously. We have correlated the GFR values with parameters of metabolic control over the last 3 years and with age, sex, and duration of diabetes. RESULTS: Patients with a GFR greater than the 95 degrees percentile value of controls (135 ml/min/1,73 m2) were defined as hyperfiltering. They represented the 55.9% (99/177) of our population. We found a strong correlation between GFR and ERPF (p <0.001), and between GFR and average HbA1c levels (p = 0.016) in multiple regression analysis, with age, sex, ERPF, and average HbA1c levels entered as variables (r2 = 0.45). There appeared to be no correlation with the duration of the disease. CONCLUSIONS: Long-term hyperglycemia provides a significant contribution in GFR and a poor metabolic control is predictive of overt nephropathy. In this study hyperfiltration does not appear to be the major factor of diabetic nephropathy. A follow-up of these patients is necessary to clarify the role of hyperfiltration in the development of overt nephropathy in diabetes.

Adult↗
PubMed1997

Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM.

Oxidative stress is postulated to be increased in patients with IDDM. Accumulating evidence suggests that oxidative cell injury caused by free radicals contributes to the development of IDDM complications. On the other side, a decreased efficiency of antioxidant defenses (both enzymatic and nonenzymatic) seems to correlate with the severity of pathological tissue changes in IDDM. Thus, we determined plasma antioxidant defenses, measuring the total radical-trapping antioxidant capacity (TRAP) and the two markers of oxidative stress, lipid hydroperoxides (ROOHs) and conjugated dienes, in 72 patients with well-controlled IDDM and without evident complications, compared with 45 nondiabetic subjects. Compared with control subjects, IDDM patients showed significantly reduced plasma TRAP (669 +/- 131 vs. 955 +/- 104 micromol/l, P < 0.001) and significantly increased levels of ROOHs (7.13 +/- 2.11 vs. 2.10 +/- 0.71 micromol/l, P < 0.001) and conjugated dienes (0.0368 +/- 0.0027 vs. 0.0328 +/- 0.0023 arbitrary units [AU], P < 0.01), especially in the trans-trans conformation (0.0340 +/- 0.0028 vs. 0.0259 +/- 0.0022 AU, P < 0.001), with a concurrent reduction of conjugated dienes in the cis-trans conformation (0.0028 +/- 0.0011 vs. 0.0069 +/- 0.0012 AU, P < 0.001). The oxidative parameters studied did not appear to be correlated with metabolic control (HbA1c levels) and lipid profile (cholesterol or triglyceride levels). The reduced TRAP and the increased ROOH and conjugated diene plasma levels, together with the decreased ratio of cis-trans/trans-trans conjugated dienes, which reflects an altered redox status of plasma, indicate that in IDDM patients, oxidative stress is enhanced and antioxidant defenses are defective, regardless of diabetes duration, metabolic control, or presence of complications.

Adult↗
PubMed1997

Cochlear dysfunction in IDDM patients with subclinical peripheral neuropathy.

OBJECTIVE: To investigate the function of the auditory pathway from the cochlea to the auditory cortex in subjects with IDDM. RESEARCH DESIGN AND METHODS: Brain stem, middle-, and long-latency auditory-evoked responses and evoked otoacoustic emissions were measured in 48 normally hearing IDDM patients and in age- and sex-matched nondiabetic subjects. Peripheral neuropathy was diagnosed by nerve conduction velocity (NCV) at the peroneal and sural nerves. Auditory brain stem responses (ABRs) reflect auditory pathway function within the brain stem; middle-latency responses (MLRs) and long-latency responses (LLRs) originate from the auditory cortex; and evoked otoacoustic emissions (EOAEs) give objective information about preneural, mechanical elements of the cochlear function. RESULTS: A subclinical peripheral neuropathy was found in 12 diabetic patients. We found higher latencies of waves I (t = 4.4, P < 0.0001), III (t = 3.7, P = 0.0004), and V (t = 2.7, P = 0.008) of ABRs in diabetic patients (I: 1.7 +/- 0.13 ms; III: 3.9 +/- 0.17 ms; V: 5.7 +/- 0.24 ms), compared with those of the control group (I: 1.6 +/- 0.13 ms; III: 3.7 +/- 0.18 ms; V: 5.6 +/- 0.17 ms). However, neither central transmission time (i.e., the wave interpeak I-V) nor MLRs and LLRs were found to be significantly different in diabetic and control subjects. Mean EOAE amplitude was found to be significantly reduced (F = 4.2, P = 0.02) in diabetic patients with a reduced NCV (7.6 +/- 3.9 dB; Scheffé test: P = 0.03), but not in those without neuropathy (9.1 +/- 4.2 dB), compared with the control group (10.8 +/- 3.1 dB). No correlations were found between duration of diabetes and EOAEs or between sural NCV and peroneal NCV and metabolic control. EOAEs were not correlated with peroneal and sural NCVs. CONCLUSIONS: Our results indicate that the early preneural dysfunction of cochlear receptors causes a prolonged activation of the peripheral portion of the auditory pathway, while signal conduction along the central auditory pathway was shown to be normal in diabetes.

Adult↗
PubMed1997

A multicenter study on the prevalence of diabetic neuropathy in Italy. Italian Diabetic Neuropathy Committee.

OBJECTIVE: The prevalence of neuropathy, a common complication of diabetes, was determined in diabetic patients recruited from 109 outpatient diabetes clinics in Italy. RESEARCH DESIGN AND METHODS: Neuropathy was diagnosed using the Diabetic Neuropathy Index (DNI), a standardized examination developed for use in the outpatient setting. A total of 8,757 diabetic patients were studied, 51.2% men and 48.8% women, with average and median ages of 56 and 58 years, respectively. RESULTS: Of the 8,757 patients, 32.3% had neuropathy, defined as a positive score of > 2 points on the DNI. A total of 2,033 (49.6% men and 50.4% women) were administered the Diabetic Neuropathy Score (DNS), the second component of the screening program, by a neurologist. This component consists of a quantitative neurological examination and nerve conduction studies that together provide a summated score. A total of 335 patients (16.5%) were not neuropathic, and 395 (19.4%) had borderline, 453 (22.3%) mild, 592 (29.1%) moderate, and 258 (12.7%) severe neuropathy. The concordance between a positive score on the DNI and a DNS indicating neuropathy was 83.5%. The severity of neuropathy increased with both age and disease duration. Of patients with neuropathy, 64.1% had an average age between 58 and 59 years with a disease duration between 12.4 +/- 8.4 years (mild neuropathy) and 15.6 +/- 9.7 years (severe neuropathy). CONCLUSIONS: Neuropathy is a common complication of diabetes and, in this study, was present in 32.3% of all patients. An increased awareness of the high prevalence of neuropathy can lead to early therapeutic intervention and possible prevention of later neuropathic complications, such as infection and foot ulcers.

Adult↗
PubMed1997

Hormonal Secretion of Nurses Engaged in Fast-rotating Shift Systems.

The aim of the study was to assess whether fast-rotating shift systems, including one or two consecutive night shifts, would cause significant disturbances of the normal hormonal patterns of ten young female nurses working in an intensive care unit. Plasma cortisol, serum prolactin, and growth hormone were measured at the start, middle, and end of one morning (07-14), one afternoon (14-21), and two night shifts (21-07); urinary excretion rates of 6-sulfatoxymelatonin (aMT6s), adrenaline (epinephrine) and noradrenaline (norephinephrine) were determined for each half of the four shifts. During the night shifts, the hormones more sensitive to exogenous components, such as catecholamines, prolactin, and growth hormone, showed an immediate response to the shifted sleep/activity cycle, evidencing a "masking effect" due to the work activity. On the other hand, hormones having stronger endogenous components, such as cortisol and melatonin, showed a more stable pattern, with a slight tendency for partial adjustment of cortisol during the second night.

Journal Article↗
PubMed1996

Prevalence of coeliac disease in type I diabetes: a multicentre study.

UNLABELLED: The aim of this study was to point out the prevalence ratio and the clinical presentation of coeliac disease (CD) in a large group of insulin-dependent diabetes mellitus (IDDM) patients. PATIENTS AND METHODS: 1114 patients affected by IDDM were screened for CD using antigliadin and antiendomysium antibodies. Patients who were positive for at least one test underwent an endoscopic biopsy of the descending duodenum in order to verify the presence of villous atrophy. Subjects with CD started a gluten-free diet and underwent a clinical follow up. RESULTS: Villous atrophy was found in 63 patients (5.6%). Among the Italian population, the rate was 7%. Twenty-four percent of coeliac patients presented with diarrhoea, while 22% were completely symptom-free. A significant correlation was found between the presence of villous atrophy and the duration and onset of diabetes. CONCLUSIONS: The prevalence of CD in IDDM is higher than previously reported, although the ratio range in different centres from 1.7 to 10%, probably due to both environmental and genetic factors. Twenty-two percent of coeliac patients were completely symptom-free. The prevalence seems to be significantly related to the duration and onset of IDDM.

Adolescent↗
PubMed1996

Postural variations of pulmonary diffusing capacity in insulin-dependent diabetes mellitus.

STUDY OBJECTIVE: To assess whether posture-related changes of diffusing capacity could be considered as an early sensitive marker of pulmonary abnormalities in patients with insulin-dependent diabetes mellitus (IDDM) and whether the postural variations of pulmonary capillary blood volume (Vc) could reflect the lung capillary damage that characterizes the diabetic microangiopathy. DESIGN: Carbon monoxide diffusing capacity (DCO) was measured by the single-breath method. Four DCO measurements, two in sitting and two in supine position, were performed in each subject using gas mixtures containing different oxygen concentrations. Membrane and capillary volume components of the diffusion capacity were calculated and both were expressed as absolute value and corrected by alveolar volume (VA). PATIENTS: Twenty IDDM patients and 20 normal subjects matched for age and sex were studied. MEASUREMENTS AND RESULTS: The IDDM patients showed normal pulmonary volumes and flows. No significant differences between the two groups were found for DCO, coefficient of diffusion, Vc, and pulmonary capillary blood volume corrected by alveolar volume in sitting position. All these indexes significantly increased in normal subjects but not in diabetics, by changing the posture of the subject from sitting to supine position. In a multivariate analysis, the presence of diabetes mellitus and the age of the subjects were the only significant predictors of Vc postural changes. CONCLUSIONS: This postural test, adjusted for age, could be included in a screening diagnostic procedure for an early assessment of pulmonary abnormalities in diabetic patients. The lack of Vc postural increase in diabetics could reflect the presence of a microangiopathy involving the pulmonary small vessels.

Adult↗
PubMed1996

NA+/K+ ATPase impairment and experimental glycation: the role of glucose autoxidation.

Non enzymatic glycation could be involved in the early impairment of Na+/K+ ATPase that occurs in sciatic nerve of diabetic rats. In fact, decrease of Na+/K+ ATPase activity is one of the first alterations showed in experimental diabetic neuropathy. In this respect, it is known that in the presence of transition metals under physiological conditions, glucose can autoxidize yielding hydrogen peroxide (H2O2) and free radical intermediates, which, in turn, inhibit the cation pump. Our experiments were designed to determine if glucose autoxidation has any relevance in the early steps of Na+/K+ ATPase experimental glycation. Compared experiments with and without the sodium borohydride (NaBH4) reduction step demonstrated that incubation of brain Na+/K+ ATPase with glucose 6-phosphate (G 6-P) and trace metals induced a significant decrease in enzyme activity dramatically enhanced by addition of copper (Cu2+). A concomitant production of H2O2 was noticed. The presence of diethylenetriaminepentaacetic acid (DTPA), a strong metal chelator, completely prevented Na+/K+ ATPase impairment and hydrogen-peroxide formation. No gross structural and conformational alterations of the enzyme can be demonstrated by intrinsic and extrinsic fluorescence measurements. Our results suggest that during the exposure of brain NA+/K+ ATPase to glucose 6-phosphate in vitro (experimental glycation), the decrease in activity can be correlated, at lease in the early phases, to metal-catalyzed production of oxidative species, such as H2O2, through the glucose autoxidation process, and not to glucose attachment to the enzyme. Since plasma hydroperoxides and copper appear to be elevated in diabetic patients with complications, our data suggest a critical role for oxidative reactions in the pathophysiology of the chronic complications of diabetes like neuropathy.

Animals↗
PubMed1995

Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus.

To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion.

Diabetes Mellitus, Type 2↗