Publications by authors named "John I Malone"

19 Publications

  • Page 1 of 1

An Observational Study of the Equivalence of Age and Duration of Diabetes to Glycemic Control Relative to the Risk of Complications in the Combined Cohorts of the DCCT/EDIC Study.

Diabetes Care 2020 10 11;43(10):2478-2484. Epub 2020 Aug 11.

University of Michigan, Ann Arbor, MI.

Objective: This epidemiological analysis of the pooled Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort describes the equivalence of a 1-percentage point increase in HbA (such as from 7% to 8%) and years of additional age or duration of type 1 diabetes (T1D) relative to the risk of complications.

Research Design And Methods: Separate Cox proportional hazards models determined the number of additional years of age and/or duration of T1D that would result in the same increase in risk of microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications and mortality as a 1-percentage point increase in HbA.

Results: The risk of any cardiovascular disease associated with a 1-percentage point increase in HbA was equivalent to the risk associated with 4.3 (95% CI 2.7-5.9) additional years of age or 5.6 (95% CI 2.7-6.5) additional years' duration of T1D. The risk of estimated glomerular filtration rate <60 mL/min/1.73 m and/or end-stage renal disease associated with a 1-percentage point increase in HbA was equivalent to the risk associated with 12.1 (95% CI 8.3-15.9) additional years of age or 18.0 (95% CI 4.3-31.7) additional years' duration of T1D. The proliferative diabetic retinopathy risk associated with a 1-percentage point increase in HbA was equivalent to the risk associated with 6.4 (95% CI 5.3-7.4) additional years' duration of T1D, while for mortality risk, it was equivalent to the risk associated with 12.9 (95% CI 6.6-19.3) additional years of age.

Conclusions: Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-0226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510046PMC
October 2020

Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite?

Pediatr Diabetes 2019 02 5;20(1):5-9. Epub 2018 Nov 5.

Department of Medicine, Morsani College of Medicine, University of South Florida, Florida.

Obesity is believed to be a promoter of type 2 diabetes mellitus (T2DM). Reports indicate that severe obesity in childhood and adolescence increases the risk of T2DM in youth and young adults. T2DM, which is commonly asymptomatic, frequently is not recognized until random blood glucose is measured. Screening blood glucose levels measured in obese individuals are more effective for identifying undiagnosed persons, than screening the general population and therefore introduces a selection bias for discovery. The following commentary will indicate why these observations do not indicate that obesity is the cause of T2DM. Also, it will be shown that the insulin resistance of T2DM occurs primarily in the muscles of lean individuals predisposed to diabetes before they become obese. This insulin resistance is not secondary to, but instead, is the cause of the excessive fat accumulation associated with T2DM. Moreover, this early muscle insulin resistance is the etiology of the hyperlipidemia and excess fat accumulation characteristic of T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pedi.12787DOI Listing
February 2019

Diabetic Central Neuropathy: CNS Damage Related to Hyperglycemia.

Authors:
John I Malone

Diabetes 2016 Feb;65(2):355-7

Morsani College of Medicine, University of South Florida, Tampa, FL

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dbi15-0034DOI Listing
February 2016

Problems with the new born screen for galactosaemia.

BMJ Case Rep 2011 Jun 3;2011. Epub 2011 Jun 3.

Department of Pediatrics, University of South Florida, Tampa, Florida, USA.

The new born screen should identify asymptomatic children with a devastating disorder before the damage has occurred. One family had two children born with classical galactosaemia. The first child, subject to a flaw in the newborn screening program, was not detected, went into rapid liver failure and ultimately had a liver transplant. The second child was following the same devastating course when identified by the new born screen with reduced galactose-1-phosphate uridyl transferase activity in a blood spot. The rapid response of the second child to removal of lactose and galactose from the diet resulted in significant clinical improvement. If the screening test for an inborn genetic defect involves the measurement of enzyme activity in red blood cells, be sure the patient has only native red blood cells. The events leading to the failure of the galactosaemia screening test are reviewed, so physicians will be aware and avoid this problem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr.01.2011.3769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109760PMC
June 2011

Tetrahydrobiopterin therapy for phenylketonuria in infants and young children.

J Pediatr 2011 Mar;158(3):410-5

Department of Pediatrics, Northwestern University Feinberg School of Medicine and PKU Clinic, Children's Memorial Hospital, Chicago, IL 60614-3363, USA.

Objective: To describe patient selection, treatment administration, response evaluation, and side effect management associated with sapropterin therapy in infants and children aged <4 years.

Study Design: Six case reports are presented from 4 US metabolic clinics treating phenylketonuria with sapropterin in patients aged 7 months to 4 years. Outcomes included blood phenylalanine (Phe) levels before and during treatment. For 3 of 6 cases, diet records were used to monitor changes in dietary Phe.

Results: Severity of phenylketonuria ranged from mild to severe (classic). Treatment with sapropterin was safe and generally well tolerated. Blood Phe levels were reduced, or maximum dietary Phe tolerance was increased in patients with blood Phe that was well controlled by diet.

Conclusions: Given the increasing evidence that maintaining blood Phe levels below 360 ╬╝mol/L is important for the normal development of neurocognitive and behavioral function, sapropterin can be combined with a Phe-restricted diet to control blood Phe levels in young patients responsive to sapropterin therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2010.08.016DOI Listing
March 2011

Microneedle-based automated therapy for diabetes mellitus.

J Diabetes Sci Technol 2008 Nov;2(6):1122-9

Department of Electrical Engineering, University of South Florida, Tampa, Florida, USA.

This article discusses the use of microneedles in automated diabetes therapy systems. Advanced bioengineered systems have the potential to close the loop between diagnostic and therapeutic elements of diabetes treatment, thus constituting a "smart" system. Prevalent insulin therapies, and most glucose sensing techniques, involve the transfer of physical entities through the skin. Micromachined needles (microneedles) can achieve this in a noninvasive or minimally invasive manner while contributing various other technological merits. The dynamics of autonomous diabetes therapy systems include highly complex interdependencies between the various physical and biological entities involved, thus warranting multidisciplinary research initiatives. The iterative development of a noninvasive, bioengineered interface such as microneedles necessitates a better understanding of the human skin, its molecular architecture as a polymer film, and its role as a functional biological unit. This review addresses application-specific requirements of a microneedle-based interface system specifically for autonomous diabetes therapy. Key design issues and related parametric interdependencies specific to this application are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769816PMC
http://dx.doi.org/10.1177/193229680800200621DOI Listing
November 2008

Effect of a brief, regular telephone intervention by paraprofessionals for type 2 diabetes.

J Behav Med 2009 Aug 14;32(4):349-59. Epub 2009 Apr 14.

Department of Psychology, University of South Florida, 4202 E. Fowler Avenue, PCD 4118-G, Tampa, FL 33620, USA.

Brief, cost-effective interventions to promote diabetes self-management are needed. This study evaluated the effects of a brief, regular, proactive, telephone "coaching" intervention delivered by paraprofessionals on diabetes adherence, glycemic control, diabetes-related medical symptoms, and depressive symptoms. Therapeutic mechanisms underlying the intervention's effect on the primary outcomes were also examined. Adults diagnosed with type 2 diabetes (N = 62) were randomly assigned to receive the "coaching" intervention and treatment as usual, or only treatment as usual. The intervention increased frequency of exercise and feet inspection, improved diet, reduced diabetes medical symptoms, and lowered depressive symptoms. Self-efficacy, reinforcement, and awareness of self-care goals mediated the treatment effect on depression, exercise, and feet inspection, respectively. A brief telephone intervention delivered by paraprofessionals had positive effects on type 2 diabetes patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10865-009-9209-4DOI Listing
August 2009

Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory.

Pediatr Diabetes 2008 Dec;9(6):531-9

Department of Pediatrics, University of South Florida College of Medicine, Tampa, FL, USA.

Background/objective: We previously reported that chronic hyperglycemia, but not hypoglycemia, was associated with the reduction of neuronal size in the rat brain. We hypothesized that hyperglycemia-induced changes in neuronal structure would have negative consequences, such as impaired learning and memory. We therefore assessed the effects of hyperglycemia and hypoglycemia on neuronal dendritic structure and cognitive functioning in young rats.

Design/methods: Experimental manipulations were conducted on male Wistar rats for 8 wk, beginning at 4 wk of age. At the completion of the treatments, all rats were trained in the radial-arm water maze, a spatial (hippocampus-dependent) learning and memory task. Three groups of rats were tested: an untreated control group, a streptozotocin-induced diabetic (STZ-D) group, and an intermittent hypoglycemic group. Following behavioral training, the brains of all animals were examined with histologic and biochemical measurements.

Results: Peripheral hyperglycemia was associated with significant increases in brain sorbitol (7.5 +/- 1.6 vs. 5.84 +/- 1.0 microM/mg) and inositol (9.6 +/- 1.4 vs. 7.1 +/- 1.1 microM/mg) and reduced taurine (0.65 +/- 0.1 vs. 1.3 +/- 0.1 mg/mg). Histologic evaluation revealed neurons with reduced dendritic branching and spine density in STZ-D rats but not in control or hypoglycemic animals. In addition, the STZ-D group exhibited impaired performance on the water maze memory test.

Conclusions: Hyperglycemia, but not hypoglycemia, was associated with adverse effects on the brain polyol pathway activity, neuronal structural changes, and impaired long-term spatial memory. This finding suggests that the hyperglycemic component of diabetes mellitus has a greater adverse effect on brain functioning than does intermittent hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1399-5448.2008.00431.xDOI Listing
December 2008

Diabetes-induced bradycardia is an intrinsic metabolic defect reversed by carnitine.

Metabolism 2007 Aug;56(8):1118-23

Julia Parrish Diabetes Research Institute, University of South Florida College of Medicine, Tampa, FL 33612-4742, USA.

Rats with streptozotocin-induced diabetes (STZ-D) have reduced serum carnitine levels and bradycardia. Heart rates (HRs) of 24nondiabetic rats (NRs) and 24 STZ-D rats were compared. L-carnitine (C) was added to the drinking water of rats (12 STZ-D+C) to raise their serum carnitine level. The intrinsic HR for each animal was determined after parasympathetic and sympathetic blockade. The HRs of STZ-D rats (278+/-15 beats per minute) were less than those of NRs (348+/-8 beats per minute) (P<.01). STZ-D rats had low serum carnitine compared with control and STZ-D+C rats. The difference in HR of STZ-D rats and NRs continued after blockade, indicating that the bradycardia ofdiabetes is intrinsic to the heart. The metabolic milieu reflected in the rats' urinary organic acid profiles differed between the control and STZ-D rats. The HR of STZ-D+C rats (326+/-5 beats per minute) did not differ from those of NRs. Increasing either the insulin dose or the serum free carnitine reduced urinary organic acids, but normal HRs were associated only with elevated serum carnitine levels. When glucose is compromised as a myocardial energy source (diabetes mellitus), we propose that elevated levels of serum carnitine may increase myocardial fatty acid metabolism sufficiently to correct the bradycardia of STZ-D rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2007.04.005DOI Listing
August 2007

Hyperglycemic brain injury in the rat.

Brain Res 2006 Mar 17;1076(1):9-15. Epub 2006 Feb 17.

Department of Pediatrics, College of Medicine, University of South Florida, Tampa, FL 33612, USA.

Children with diabetes onset before 5 years of age have reduced neurocognitive function. This problem has been attributed to hypoglycemia, a complication of insulin therapy. The eye, kidney, and nerve complications of diabetes (hyperglycemia) have been reduced by intensified insulin therapy which is associated with a 3-fold increase in severe hypoglycemia and therefore is not recommended for children less than 13 years of age. Since hyperglycemia is much more common than intermittent hypoglycemia during early childhood diabetes, it is important to determine if hyperglycemia affects brain growth and development. Rats were exposed to 4 weeks of either continuous hyperglycemia (diabetes) or intermittent (3 h, 3 times/week) hypoglycemia from 4 to 8 weeks of age. The brains of these animals were compared to those of similarly aged normal control animals. The cell number was increased, and the cell size reduced in the cortex of diabetic animals as assessed by DNA/wet weight of brain and protein/DNA content. Reduced amounts of protein, fatty acids, and cholesterol/microgram DNA also indicate smaller cells with reduced myelin content in the cortex of the diabetic animals. Histologic evaluation of these brains confirmed the biochemical findings. These observations require further confirmation and evaluation but indicate that continuous hyperglycemia may be more damaging than intermittent hypoglycemia to the developing brain. This is an important consideration for the management of diabetes mellitus in young children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2005.12.072DOI Listing
March 2006

Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats.

Cardiovasc Diabetol 2006 Jan 19;5. Epub 2006 Jan 19.

The Department of Pediatrics, University of South Florida, College of Medicine, Tampa, FL 33612, USA.

Background: Streptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement.

Aim: The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats.

Methods: Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks.

Results: The heart rates for the STZ-D rats (290 +/- 19 bpm) were less than control rats (324 +/- 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 +/- 8 bpm) was greater than controls (79 +/- 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 +/- 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 +/- 0.5) was greater than control animals (2.2 +/- 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 +/- .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks.

Conclusion: Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1475-2840-5-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1363717PMC
January 2006

Issues and advances in childhood diabetes.

Authors:
John I Malone

Adv Pediatr 2004 ;51:111-29

Diabetes Center, University of South Florida, Tampa, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
October 2004

Tests of glycemia in diabetes.

Diabetes Care 2004 Jul;27(7):1761-73

Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65212, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/diacare.27.7.1761DOI Listing
July 2004

A brief, regular, proactive telephone "coaching" intervention for diabetes: rationale, description, and preliminary results.

J Diabetes Complications 2004 Mar-Apr;18(2):113-8

Department of Psychology, PCD 4118G, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA.

Telephone-delivered interventions (TDIs) represent a potentially cost-effective method to increase medical adherence. TDIs for diabetes patients have typically been delivered by nurses or computerized telephone messaging. Psychology undergraduates, however, are less costly than nurses, have a strong background in behavioral science, and provide the personal relationship missing with computerized contact. This paper presents the rationale for and description of a brief, regular, proactive telephone intervention designed to be delivered by psychology undergraduates (i.e., paraprofessionals). "Coaches" administer a 15-min telephone intervention weekly for 3 months and biweekly for 3 additional months. Guided by a semistructured protocol that focuses on behavioral goals, coaches provides support, collaborative problem-solving, and apply basic cognitive-behavioral techniques. Results from a pilot study on type 1 diabetes patients are presented. This preliminary evidence suggests that the program is feasible, acceptable to a large majority of patients, and effective in reducing HbA1c levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1056-8727(02)00254-4DOI Listing
December 2004

Type 2 diabetes mellitus among Florida children and adolescents, 1994 through 1998.

Public Health Rep 2002 Jul-Aug;117(4):373-9

University of South Florida, Tampa, FL, USA.

Objectives: This study was undertaken to examine the trends in the diagnosis of Type 2 diabetes mellitus among children and adolescents with new-onset diabetes seen from 1994 through 1998 at the three university-based diabetes centers in Florida.

Methods: Data were abstracted from medical records and patients were categorized as having Type 1 or Type 2 diabetes.

Results: There were 569 patients classified with Type 1 diabetes and 92 with Type 2 diabetes. The proportion of patients diagnosed with Type 2 diabetes increased over the five years from 9.4% in 1994 to 20.0% in 1998 (chi-square test for trend = 8.2; p=0.004). There was not an associated net increase in the total number of new diabetes patients referred over time (chi-square test for trend = 0.6, p=0.4). Those with Type 2 diabetes were more likely to have a body mass index in the 85th-94th percentile [odds ratio (OR) = 8.5; 95% confidence interval (CI) 2.5, 28.8], have a body mass index >or=95th percentile (OR = 6.8; 95% CI 2.6, 17.7), Hispanic ethnicity (OR = 6.2; 95% CI 2.2, 17.9), black race (OR = 2.8; 95% CI 1.3, 6.2), female gender (OR = 2.2; 95% CI 1.2, 4.3), and older age (OR = 1.4 for each one-year increment in age; 95% CI 1.3, 1.6), compared with those having Type 1 diabetes.

Conclusions: From 1994 through 1998, there was a significant overall increase in the percentage of children referred with new-onset diabetes who were considered to have Type 2 diabetes. Factors associated with the diagnosis of Type 2 diabetes relative to Type 1 diabetes include body mass index >/=85th percentile, Hispanic ethnicity, black race, female gender, and older age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1497443PMC
http://dx.doi.org/10.1093/phr/117.4.373DOI Listing
January 2003