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D Ellis

Publications and source records attributed to D Ellis.

At least 19 recordsLinked to original sources
PubMed1996

Incidence of complications in insulin-dependent diabetes mellitus: a survival analysis.

The authors used 4-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study to investigate the wider applicability of recent research findings that demonstrate an association between glycemic control and insulin-dependent diabetes mellitus (IDDM) complications. EDC subjects participated in clinical examination at baseline (1986-1988) and were followed up every 2 years. Results demonstrated that, during the first 4 years of follow-up, subjects who were in "poor" control (glycosylated hemoglobin (GHb) > or = 11%) at baseline were significantly (p < 0.001) more likely to develop microalbuminuria, proliferative retinopathy, and distal symmetrical polyneuropathy (DSP), compared with subjects who were in "fair" control (GHb < 11%). Subjects who were in poor control were somewhat more likely to develop overt nephropathy (p = 0.08) and renal failure (p = 0.085) during follow-up; however, no associations were observed with either coronary heart disease or lower extremity arterial disease (LEAD). These results confirm the strong association between prior glycemic control and the onset of microalbuminuria, proliferative retinopathy, and DSP observed in the Diabetes Control and Complications Trial study. However, the results of the study suggest weaker associations for the later stages of renal disease, and little relation was seen between glycemic control and LEAD or coronary disease. Other risk factors may be more important for the development of the later complications of IDDM. Further follow-up is necessary in order to rule out type II error.

Adult↗
PubMed1996

Transmembrane movement of lithium ions in isolated sheep heart Purkinje fibres.

The many routes by which Li can cross the cardiac sarcolemma were examined using Li-selective microelectrodes. In the presence of 70 mmol/l extracellular Li there was a rapid increase in intracellular Li activity (aiLi) equivalent to an influx of 0.45 mmol/l/min (or 2.1 pmol/cm2.s). Depolarisation (voltage-clamp or high [K]O) had no significant effect on the rate of aiLi increase, or recovery on removal of LiO. Following addition of 20 mmol/l [Li]O to the normal Tyrode, the rate of aiLi increase was stimulated by 49.7% by removal of extracellular Mg. However Li entry was inhibited by SITS (100 mumol/l) by 20.6%; tetrodotoxin (10(15)g/ml) 20.0%; caesium (2 mmol/l) 22.5%; verapamil (20 mumol/l) 14.3%; and manganese (1 mmol/l) 37.6%. With 5 mmol/l [Li]O, aiLi stabilized at 2.3 mmol/l, i.e. much lower than expected assuming passive distribution of Li (predicted level 61 mmol/l), implying active extrusion of Li from the cells. This stable level of Li was not significantly affected by short exposures to strophanthidin, bumetanide, or ethyl isopropylamiloride, but was decreased by increasing the [Ca]O or adding manganese. The aiLi was increased on removal of [Na]O or addition of phloretin (100 mumol/l) suggesting that NaO-Lii exchange helps to maintain a low aiLi. The removal of KO produced an increase in aiLi. This effect was inhibited by strophanthidin, suggesting Li can enter via the Na/K pump in K-free conditions.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1996

Na-dependent regulation of intracellular free magnesium concentration in isolated rat ventricular myocytes.

Changes in ionized intracellular free magnesium concentration [Mg2+]i were measured in isolated, superfused rat ventricular myocytes using mag-fura-2. Cells were superfused with media containing high or low Mg concentrations ([Mg]o), with and without Na (Nao) and/or Ca (Cao). Increasing [Mg]o from 1 to 5 mmol/l in Ca-free solutions had no significant effect on [Mg2+]i when [Na]o was normal. However, [Mg2+]i rose steadily when Nao was completely replaced by either tetramethylammonium (TMA) or K. This [Mg2+]i rise was inhibited by imipramine (10 mumol/l) but not by verapamil (25 mumol/l). [Mg2+]i returned rapidly from a high to its initial level on superfusing cells with basic medium containing normal Ca, Na and Mg. [Mg2+]i recovery required Nao and was inhibited by imipramine (10 mumol/l). When Mgo was removed from Ca-free superfusates, the [Mg2+]i decreased whether or not Nao was present. However, [Mg2+]i decreased most when Nao was replaced by K. Neither imipramine nor verapamil affected the magnitude of this fall, but verapamil slowed it. [Mg2+]i rapidly increased to normal when depleted cells were superfused with basic medium with or without Cao. Both imipramine and verapamil slowed this recovery. Superfusion of cells with Ca-free media containing strophanthidin (20 mumol/l) caused [Mg2+]i to rise, but only if the medium contained Mg (1 mmol/l). The data suggest that Mg can enter cardiac myocytes through routes which close when physiological [Mg2+]i is attained. One pathway for Mg flux is by a Na-dependent, imipramine-sensitive mechanism which is probably a Na-Mg antiport.

Animals↗
PubMed1996

The use of tacrolimus in renal transplantation.

Tacrolimus (FK 506) is a novel immunosuppressive agent that has been in clinical use for solid organ transplantation since 1989. Early clinical trials of tacrolimus in liver, heart, kidney, lung, and intestinal transplantation at the University of Pittsburgh have demonstrated it to be a safe and effective agent with several potential advantages over existing immunosuppressive drugs. More recently, phase I and II multicenter trials of tacrolimus for renal transplantation have been performed; however, data are not yet available from these trials. Our experience with this drug has demonstrated excellent 1- and 2-year actuarial graft survival rates of 89% and 83%, respectively, in adult renal transplantation and 1- and 3-year graft survival rates of 98% and 85%, respectively in pediatric renal transplantation. A major advantage of tacrolimus noted in these trials was the ability to discontinue steroid therapy in approximately 50% of the patients. Tacrolimus has also shown efficacy as a rescue agent for renal allograft rejection failing conventional therapy in 74% of cases. This paper expands on these observations and focuses on the experience we have gained with the use of tacrolimus at our institution over the last 6 years.

Graft Survival↗
PubMed1996

Intracellular pH and intrinsic H+ buffering capacity in normal and hypertrophied right ventricle of ferret heart.

OBJECTIVE: To answer the questions: (a) What is the effect of hypertrophy on the intracellular pH (pHi) and buffering power of cardiac muscle, and (b) How does hypertrophy affect the ability of cardiac muscle to recover from intracellular acidosis induced by hypoxia. METHODS: In nominally HCO3(-)-free, HEPES-buffered Tyrode solution (35 degrees C), pHi and the intrinsic buffering power (beta i, measured in the presence of amiloride) was investigated using pH-sensitive microelectrodes. RESULTS: beta i was similar in both preparations (25 mM/pH unit at pHi 7.04). beta i was inversely related to pHi but the relationship was not significantly modified by hypertrophy. In the absence of amiloride, the time constant of pHi recovery (tau r) on removal of NH+4, was similar in normal (4.0 +/- 0.2 min, n = 5) and in hypertrophied muscles (4.3 +/- 0.3 min, n = 4; n.s.). In both preparations, net acid extrusion (JH) was similarly increased at lower values of pHi. Lowering temperature from 35 degrees to 22 degrees caused an alkalinization (0.15 pH units) of pHi. At 22 degrees C the mean values of pHi, beta i, tau r and JH were similar in normal and in hypertrophied muscles. At both temperatures and in both groups of preparations, recovery of pHi following hypoxia is approximately exponential. The time constant of recovery of pHi following hypoxia (tau rh) at 22 degrees C was not significantly different in hypertrophied muscles (7.2 +/- 0.9 min, n = 8) compared to controls (10.6 +/- 1.8 min, n = 13). However, at 35 degrees C, there was a significant difference in the mean values of tau rh which was smaller for hypertrophied muscles (3.9 +/- 0.3 min, n = 7) than for normal (7.1 +/- 1.1 min, n = 4, P < 0.005). For pHi 6.8-7.0, net acid extrusion in hypertrophied preparations was increased by a factor of 4 compared to normal. CONCLUSIONS: The intracellular buffering capacity and the pHi regulating capacity via Na+/H+ exchange are not significantly modified by right ventricular hypertrophy in ferret heart. The faster pHi recovery from hypoxia-induced acidification can be interpreted in terms of the role of lactate efflux in pHi control. The possible role of energy compartmentalization, its influence on the Na+ gradient and thus on pHi control after hypoxia, is discussed.

Amiloride↗
PubMed1996

The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria.

Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 microg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by > or = 10-fold into the microalbuminuric (20 to 200 microg/min) or normal range (<20 microg/min) in 7 of these individuals and are called "regressors of proteinuria." Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors (P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 microg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change (P < 0.01), and a decrease in plasma LDL-C level (P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 mg/min) than previously reported (200 microg/min).

Adult↗
PubMed1996

Coronary artery disease in IDDM. Gender differences in risk factors but not risk.

Insulin-dependent diabetes mellitus (IDDM) increases the risk of developing coronary artery disease (CAD) compared with that seen in the general population, while the sex differential in rates of CAD is considerably reduced in IDDM populations. To further our understanding of these observations, the effects of gender on baseline risk factors for CAD incidence were examined. Participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study were recruited from the Children's Hospital of Pittsburgh IDDM registry and had been diagnosed between 1950 and 1980. Subjects completed a series of questionnaires and were given a full clinical examination at baseline (1986 through 1988) and every subsequent 2 years. This report is based on the first 4 years of follow-up. Similar incidence rates of new CAD events were observed in men and women. In neither sex was glycemic control a predictor of later CAD. Sex-specific Cox proportional hazards models showed that for men, duration of IDDM, HDL cholesterol, fibrinogen, hypertension, and smoking were all significantly associated with the onset of CAD. Hypertension, fibrinogen, and smoking were all replaced by nephropathy when this latter variable was added to the model. For women, duration, hypertension, waist-hip ratio, physical activity, and depressive symptomatology were all significant independent predictors of CAD. Nephropathy status did not enter the model for women. While 4-year incidence of CAD in IDDM varies little by sex in this population, the predictive risk factors vary considerably. In particular, the effect of renal disease was stronger in men, while the cluster of physical activity, waist-to-hip ratio, and depressive symptomatology were more important in women. These results may help explain the relatively greater impact IDDM has on CAD risk for women and suggest new potential preventive approaches.

Adolescent↗
PubMed1995

Clinical use of tacrolimus (FK-506) in infants and children with renal transplants.

Although cyclosporine (CsA)-based immunosuppressive regimens have been highly successful in renal transplantation in infants and children, their adverse influence on somatic growth, general appearance, and blood pressure are of particular importance in this population. Over the past 4 years, we have utilized tacrolimus (formerly FK-506) as the primary immunosuppressive agent in 43 unselected children and achieved 1-year and 3-year allograft survival rates of 96% and 85%, respectively. We have also used tacrolimus to rescue 14 of 19 (74%) renal allografts from CsA-resistant rejection. Corticosteroids were discontinued in 62% of non-rescue patients without increasing the risk of rejection or renal dysfunction over a mean follow-up time of 25 months. Tacrolimus monotherapy has been associated with improved body growth and less obesity, while tacrolimus alone or in combination with prednisone was virtually free of hirsutism or gingival hypertrophy, and posed a low risk for hypertension. A major disadvantage of this regimen may be an increased risk for viral infections and a benign form of posttransplant lymphoproliferative disease. This article describes the tacrolimus protocol utilized in our center and focuses on practical clinical issues including therapeutic monitoring, benefits, and major toxicity in children with renal allografts.

Child↗
PubMed1995

FK506 in pediatric kidney transplantation--primary and rescue experience.

Between 14 December 1989 and 17 December 1993, 43 patients undergoing kidney transplantation alone at the Children's Hospital of Pittsburgh received FK506 as the primary immunosuppressive agent. The mean recipient age was 10.2 +/- 4.8 years (range 0.7-17.4 years), with 7 (16%) children under 5 years of age and 2 (5%) under 2 years of age. Fifteen (35%) children underwent retransplantation, and 5 (12%) had a panel-reactive antibody level greater than 40%. Twenty-two (51%) transplants were with cadaveric donors and 21 (49%) were with living donors. The mean follow-up was 25 +/- 14 months; there were no deaths; 1- and 3-year actuarial graft survival was 98% and 85%. The mean serum creatinine and blood urea nitrogen were 1.2 +/- 0.6 mg/dl and 26 +/- 11 mg/dl; the calculated creatinine clearance was 75 +/- 23 ml/min per 1.73 m2. Twenty-four (62%) patients have been successfully withdrawn from steroids and 24 (62%) require no anti-hypertensive medication. Improved growth was seen, particularly in pre-adolescent children off steroids. Between 28 July 1990 and 2 December 1993, 24 children were referred for rescue therapy with FK506, 14.6 +/- 16.4 months (range 1.1-53.2 months) after transplantation. Nineteen (79%) were referred because of resistant rejection; 4 (17%) were referred because of proteinuria; 1 (4%) was switched because of steroid-related obesity. There were no deaths; 1- and 2-year graft survival was 75% and 68%; 17 (71%) patients were successfully rescued, including 1 of 2 patients who arrived on dialysis; 4 (24%) of the successfully rescued patients were weaned off steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Evaluation and management of bilateral renal artery stenosis in children: a case series and review.

This report describes the clinical course, diagnostic evaluation and management of six children with bilateral renal artery stenosis (RAS) and concurrent narrowing of the abdominal aorta. Except for one child with active arteritis, the others were asymptomatic. There were no clinical or laboratory features suggesting the etiology of hypertension in four of six patients, and diagnostic procedures, including Doppler duplex ultrasound and captopril scintigraphy, were unreliable in screening for such hypertension. Abdominal aortography and selective renal angiography confirmed the diagnosis of bilateral RAS and associated anatomical alterations of the aorta and its branches. The hypertension was severe and minimally responsive to antihypertensive agents. It was cured or improved after percutaneous transluminal angioplasty (PTA) of three vessels in two children with mid-vessel stenoses, while hypertension persisted after PTA of two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a fourth child. Autotransplantation of seven kidneys in four children resulted in cure of significant improvement of the hypertension. Renal function was preserved in all children during a mean follow-up time of 41 months. Based on illustrative data from these six children, as well as information from a review of the literature, this report discusses the key diagnostic issues and stresses the potential advantages of renal autotransplantation in selected children with this disorder.

Adolescent↗
PubMed1995

Intracellular pH during hypoxia in normal and hypertrophied right ventricle of ferret heart.

The effects of preventing oxidative phosphorylation on pHi were compared in papillary muscles from right ventricles of normal and pressure-overloaded ferret hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days. pHi was recorded with pH-sensitive microelectrodes. Resting pHi and the relationship between intracellular buffering power and pHi were not modified by the hypertrophy. At 22 degrees C, the initial intracellular alkalosis following exposure to oxygen-free Tyrode solution (containing the reducing agent sodium dithionite, 1 mM), as well as the transient acidosis on return to oxygenated solution, were reduced in hypertrophied papillary muscles. During hypoxia, exposure to alpha-cyano-4-hydroxycinnamate (5 mM) induced a larger intracellular acidification in hypertrophied than in control muscle. The initial alkalosis during hypoxia and the extra acidification on recovery from hypoxia were also significantly reduced in hypertrophied muscles at 35 degrees C. Moreover, the acidification during hypoxia was markedly accentuated in hypertrophied preparations at this temperature. [Mg2+]i and [Ca2+]i were also measured during metabolic inhibition, using mag-fura-2 and fura-2 respectively, in isolated cells from control and hypertrophied right ventricles. Hypertrophy increased the resting level of [Ca2+]i and of [Mg2+]i by a factor of 2.5 (P < 0.001) and 1.3 (P < 0.05) respectively. Upon application of 15 mM 2-deoxyglucose, [Mg2+]i was increased to a similar extent in control and hypertrophied cells. It is concluded that right ventricular hypertrophy could modify creatine phosphate metabolism and the capacity to recruit anaerobic glycolysis.

Animals↗
PubMed1995

Personality disorder and sexual risk taking among homosexually active and heterosexually active men attending a genito-urinary medicine clinic.

61 homosexually active men and 57 heterosexually active men attending a genito-urinary medicine clinic were assessed for personality disorder and sexual risk taking. Of the homosexually active men, 23/61 (38%) were found to have personality disorders, as against 16/57 (28%) of the heterosexually active men. Multiple regression analysis indicated that antisocial personality disorder (p < 0.001) was the main predictor of sexual risk taking for the homosexually active clinic attenders. In the case of the heterosexually active men attending the clinic, sexual risk taking was predicted by cocaine use (p < 0.001) and antisocial personality disorder (p < 0.001). These results indicate a need to screen for personality disorders in genitourinary medicine clinics and at the time of pre-HIV test counseling.

Adolescent↗
PubMed1995

High mortality from unidentified CVD in IDDM: time to start screening?

Mortality in insulin-dependent diabetes is markedly increased compared to the general population. Although strong associations have been found between renal disease and the risk of cardiovascular disease (CVD) the interaction between these two factors is not well understood. This study, which addresses risk factors for mortality in IDDM with a particular focus on the renal-CVD link, is based on the prospective Epidemiology of Diabetes Complications study. Thirty-seven (mean age 36 years, mean duration of IDDM 28 years at baseline) of the 658 IDDM individuals (mean age 28 years, mean duration of IDDM 20 years at baseline) have died in the first 4 years of follow up. A nested case-control study was performed, matching on sex and duration of diabetes. Twenty-two (59%) of the deaths were attributed to coronary heart disease, with an additional 16% attributed to diabetic coma. Only nine (41%) of the 22 individuals who died from cardiovascular disease had clinical evidence of coronary heart disease when seen for their last biennial exam. However, 54% of those who died of CVD without prior evidence did have evidence of lower extremity arterial disease. A strong link with renal disease was confirmed, with 81% of those with a coronary artery disease death having renal disease. Multivariate analyses suggest that smoking history, triglycerides and total platelet count are independent predictors of mortality, while LDL cholesterol best predicted CVD mortality. These results suggest a need for more intensive screening for cardiovascular disease, and correction of cardiovascular risk factors, in order to reduce the increased rate of mortality in this population. Efforts to prevent or delay the onset of renal disease may also be of benefit.

Adult↗
PubMed1995

Terbinafine in onychomycosis of the toenail: a novel treatment protocol.

BACKGROUND: Current treatment of onychomycosis of the toenail is poor and relapse is common. OBJECTIVE: Our purpose was to assess the efficacy and safety of oral terbinafine and placebo in onychomycosis of the toenail with the use of a novel treatment protocol. METHODS: This was a randomized, double-blind, 48-week study. Twelve weeks of terbinafine (250 mg daily) or placebo was followed by 12 weeks of observation. Responders received no further treatment and nonresponders were offered 12 weeks of terbinafine (250 mg daily) from week 28. RESULTS: Of 111 evaluable patients, 88% (49 of 56) of the patients given terbinafine and 29% (16 of 55) of the patients given placebo had a negative mycologic culture at week 24 (p < 0.001), 57% (32 of 56) of the terbinafine group and 6% (3 of 55) of the placebo group were responders (p < 0.001). By week 48, after the terbinafine nonresponders were given a second 12-week course of terbinafine, the overall mycologic cure rate for the patients given terbinafine was 94%. CONCLUSION: High mycologic cure rates in onychomycosis of the toenail can be achieved by terbinafine by this novel treatment regimen.

Adolescent↗
PubMed1995

A case of Pelizaeus-Merzbacher disease showing increased dosage of the proteolipid protein gene.

Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial and spinal root myelin was preserved. Probes for cDNA in the boy and his asymptomatic mother indicated an increase in the dosage of proteolipid protein gene (of at least twofold) compared with controls.

DNA Probes↗
PubMed1995

Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity.

Hyperlipidemia has been implicated in the pathogenesis of experimental progressive glomerulosclerosis, but its role in human renal injury is controversial. This report describes a 12-yr-old boy presenting with massive proteinuria, hepatomegaly, anemia, severe mixed hyperlipidemia, and progressive renal failure. The initial renal biopsy disclosed large numbers of foam cells that were shown to be monocytes. Evidence is presented suggesting that apoprotein-E2 homozygosity in our patient, together with an 88% reduction in plasma lipoprotein lipase activity associated with severe nephrotic syndrome, is responsible for the atypical clinical features, lipoprotein phenotype III with chylomicronemia, and renal lipidosis. A regimen of dietary lipid restriction, gemfibrozil, and niacin resulted in significant but partial improvement of the dyslipidemia and resolution of the hepatomegaly and ascites. This report stresses the importance of characterizing unique lipid disorders in patients with nephrotic syndrome in order to prescribe effective lipid-lowering strategies. Moreover, the striking resemblance of the clinical and nephrohistologic features of this patient to those occurring in experimental models of coexisting glomerular injury and hyperlipidemia led to the speculation that, in this setting, the hyperlipidemia may contribute to the development of progressive glomerulosclerosis.

Apolipoproteins E↗
PubMed1995

The influence of pregnancy on IDDM complications.

OBJECTIVE: Although pregnancy has been associated with an increased progression of certain insulin-dependent diabetes mellitus (IDDM) complications, particularly retinopathy, both the short- and long-term relationships between pregnancy and both neuropathy and macrovascular disease are poorly documented. This study was conducted to comprehensively examine the influence of pregnancy on the development and progression of IDDM complications. RESEARCH DESIGN AND METHODS: Using the Pittsburgh Epidemiology of Diabetes Complications Study population (childhood-onset IDDM), two nested, pair-matched case-control studies were conducted. Women who had completed at least one successful pregnancy (n = 80) were matched to women with no history of pregnancy by age, duration of IDDM, race, and marital history. The first nested study (study 1) compared the prevalences of five IDDM complications between case and control groups. The second nested study (study 2) compared the incidences of the same five complications over an approximate 2-year interval during which the case subjects (n = 30) completed a successful pregnancy. RESULTS: There were no significant differences in the prevalence rates of coronary heart disease, neuropathy, proliferative retinopathy, lower extremity arterial disease, and overt nephropathy by case-control status, while parity did not predict any complication in multiple logistic analysis (study 1). In study 2, there were small but nonsignificant differences in incidence rates of overt nephropathy and lower extremity arterial disease between the groups, whereas case subjects had almost 3 times the incidence rate of proliferative retinopathy (P = 0.58) and 10 times the incidence rate of neuropathy (P < 0.001) as did other matched control subjects. In multivariate analysis, parity predicted neuropathy incidence but did not predict the incidence of any other complication, including proliferative retinopathy. CONCLUSIONS: Women with IDDM who experience a pregnancy may not be at an increased risk of diabetes complications later in life. However, in the short term, pregnancy may accelerate the development of some complications, such as neuropathy.

Adult↗