The interplay between bone and heart health as reflected in medication effects: A narrative review.

There is mounting evidence of an association between osteoporosis and cardiovascular disease that extends beyond shared risk factors for these conditions. In turn, the medications used to treat each of these conditions can have effects that impact the other organ system: medications used in heart disease have the potential to affect bone health, while osteoporosis medications may modify cardiovascular health. While data in this subject area are limited by the paucity of large randomized controlled trials with bone mineral density or fracture risk as primary outcomes, this review explores the data available that can provide some insight into these reciprocal effects of medications on bone and heart health. Data on bone health effects of the loop and thiazide diuretics, beta blockers, calcium channel blockers, statins, warfarin, sodium-glucose cotransporter 2 inhibitors, metformin, and medications impacting the renin-angiotensin-aldosterone system are examined; the cardiovascular effects of osteoporosis therapies and vitamin D are also discussed. Importantly, while most data in this realm are inconclusive, recognizing the parallels between cardiovascular and bone disorders and how this is reflected in medication effects might prompt the clinician to consider the indirect impact of drug regimens when making therapeutic choices for patients with osteoporosis and heart disease.

Higher burden of cardiometabolic and socioeconomic risk factors in women with type 2 diabetes: an analysis of the Glycemic Reduction Approaches in Diabetes (GRADE) baseline cohort.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS: GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017. RESULTS: Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes. CONCLUSIONS: This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01794143).

Internal Carotid Artery Aneurysm Mimicking a Pituitary Adenoma: A Case Report and Review of the Literature.

Background/Objective: A thrombosed internal carotid artery (ICA) aneurysm mimicking a pituitary adenoma can be catastrophic if unrecognized. We report a unique case of the rare presentation of ICA aneurysms masquerading as pituitary adenomas, which can preserve pituitary function when treated early. Case Report: A 54-year-old man with type 2 diabetes, aortic valve replacement, and stroke presented with sudden onset severe headache and left eye pain. Left third nerve palsy was noted. Laboratory studies showed low thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, testosterone, and insulin-like growth factor 1 levels and baseline, post-30-minute, and post-60-minute cortisol levels of 16, 17, and 14 µg/dL, respectively, after adrenocorticotropic hormone stimulation. Magnetic resonance imaging of the pituitary revealed a heterogeneously enhancing 2.0 × 2.1 × 2.1-cm sellar/suprasellar mass with peripheral enhancement abutting the left cavernous sinus. Given the acute third nerve palsy without visual defects and magnetic resonance imaging findings, other sources of sellar occupying etiology were suspected. Therefore, carotid cerebral angiography was performed and revealed a mostly thrombosed left ICA aneurysm projected into the sellar/suprasellar region. The patient underwent successful endovascular treatment with a resolution of the cranial nerve palsy and hormonal abnormalities at 3-month follow-up. Discussion: Our case demonstrates the importance of swift recognition of ICA aneurysms masquerading as pituitary adenomas. Early recognition and treatment may lead to the complete resolution of presenting symptoms and hormonal deficiencies. Conclusion: Clinicians should have a high index of suspicion for ICA aneurysm in the differential diagnosis for a sellar mass. Careful evaluation is essential because misdiagnosis may lead to catastrophic consequences.

Time-restricted eating did not alter insulin sensitivity or ß-cell function in adults with obesity: A randomized pilot study.

OBJECTIVE: Decreased insulin sensitivity and impairment of ß-cell function predate and predict development of type 2 diabetes mellitus. Time-restricted eating (TRE) might have a benefit for these parameters. The objective of this pilot study was to investigate this possibility. METHODS: Secondary analysis of a randomized controlled trial comparing 12 weeks of TRE (8-hour eating window) to unrestricted eating (non-TRE) was performed. Participants were adults with overweight or obesity and without diabetes. Two-hour oral glucose tolerance testing was performed at baseline and end-intervention. Glucose tolerance test-derived measures of insulin sensitivity, insulin secretion, and ß-cell function were compared between groups. RESULTS: Participants (17 women/3 men with mean [SD] age 45.5 [12.1] years and BMI 34.1 [7.5] kg/m2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE (n = 11) or non-TRE (n = 9). The quantitative insulin sensitivity check index (QUICKI), Stumvoll index, Avignon index, insulinogenic index, insulin area under the curve/glucose area under the curve, and oral disposition index did not differ between the TRE and non-TRE groups at end-intervention. CONCLUSIONS: In adults with overweight or obesity and without diabetes, TRE did not significantly alter insulin sensitivity, insulin secretion, or ß-cell function over a 12-week intervention. Whether TRE is beneficial in adults with prediabetes or type 2 diabetes mellitus warrants further investigation.

AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity.

BACKGROUND & AIMS: Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap. CONCLUSIONS: In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.

Reduced bone mineral density in the first year after total pancreatectomy with islet autotransplantation (TPIAT).

BACKGROUND/OBJECTIVES: The effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. METHODS: We measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. RESULTS: In the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ -2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%-4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). CONCLUSIONS: TPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.

Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis.

CONTEXT: Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied. OBJECTIVE: Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT. METHODS: In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression. RESULTS: Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (-0.05 [0.02] per extra kg; P = 0.01) and 18 months (-0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (-206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and -1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition. CONCLUSIONS: Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT.

AN ADJUNCTIVE USE OF ASFOTASE ALFA AND ZOLEDRONIC ACID AFTER SPINAL SURGERY IN NEUROFIBROMATOSIS TYPE 1 RELATED DYSTROPHIC SCOLIOSIS.

OBJECTIVE: Dystrophic scoliosis is a serious skeletal manifestation of neurofibromatosis 1 (NF1). The condition requires surgical intervention that is frequently associated with poor outcome due to the high rate of impaired bone healing, pseudoarthrosis, and loosening of the spinal instrumentation. New therapeutic approaches are needed to improve surgical outcomes. METHODS: Clinical, laboratory, and radiographic data are presented. RESULTS: A 54-year-old woman with severe NF1 related dystrophic scoliosis and 3 prior surgical interventions underwent revision of lumbar fusion with intraoperative recombinant human bone morphogenetic protein (rhBMP-2) for loosening and a fracture of the left vertical rod at the L4 pedicle screw connection. Two days after surgery, a computed tomography (CT) scan revealed a left posterior iliac periscrew fracture. Given a high risk of mechanical failure, zoledronic acid and asfotase alfa were also administered at 3 and 7 months after surgery. At 14 months after surgery, back pain improved, and a CT scan showed stable spinal fusion and a healed left posterior iliac screw fracture. CONCLUSION: Combination therapy including asfotase alfa with rhBMP-2 and bisphosphonate resulted in solid arthrodesis after spinal surgery in NF1-related dystrophic scoliosis.

Time-Restricted Eating Alters Food Intake Patterns, as Prospectively Documented by a Smartphone Application.

Time-restricted eating (TRE) can facilitate weight loss, yet its effect on eating patterns remains unknown. Twenty adults with BMI ≥ 25 kg/m2 underwent a 12-week randomized trial, examining the effect of an 8-h, time-restricted eating intervention on dietary patterns. Oral intake was documented using a smartphone. Dietary patterns, assessed as frequency of eating occasions (EOs) and types of meals/snacks and beverages, were compared between baseline (T0), early-intervention (T1), and end-intervention (T2). At T1 and T2, both groups had less EOs compared to T0, with greater reduction seen in the TRE group (-28%) than the non-TRE group (-12%) at T2 (p = 0.01 vs. non-TRE). Comparing T1 to T0, the TRE group documented less incomplete meals (-32.5%: p = 0.02), high quality snacks (-23.6%: p = 0.03), and low quality snacks (-36.6%: p = 0.004). Comparing T2 to T0, the TRE group documented less incomplete meals (-33.9%: p = 0.03), high quality snacks (-28.1%: p < 0.001) and low quality snacks (-51.2%: p < 0.001). Caffeinated beverage intake was reduced in the TRE group at T1 (-20.2%) and T2 (-28.8%) vs. T0, but remained unaltered in the non-TRE group. By using a smartphone application to document dietary intake, TRE significantly reduced the number of EOs, snacks, and caffeinated beverages, relative to baseline and relative to the non-TRE.

Time-Restricted Eating Effects on Body Composition and Metabolic Measures in Humans who are Overweight: A Feasibility Study.

OBJECTIVE: In contrast to intentionally restricting energy intake, restricting the eating window may be an option for treating obesity. By comparing time-restricted eating (TRE) with an unrestricted (non-TRE) control, it was hypothesized that TRE facilitates weight loss, alters body composition, and improves metabolic measures. METHODS: Participants (17 women and 3 men; mean [SD]: 45.5 [12.1] years; BMI 34.1 [7.5] kg/m2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE (n = 11: 8-hour window, unrestricted eating within window) versus non-TRE (n = 9: unrestricted eating) for 12 weeks. Weight, body composition (dual x-ray absorptiometry), lipids, blood pressure, 2-hour oral glucose tolerance, 2-week continuous glucose monitoring, and 2-week physical activity (actigraphy assessed) were measured during the pre- and end-intervention periods. RESULTS: The TRE group significantly reduced the eating window (end-intervention window: 9.9 [2.0] hours) compared with the non-TRE group (end-intervention window: 15.1 [1.1] hours) (P < 0.01). Compared with non-TRE, TRE decreased the number of eating occasions, weight, lean mass, and visceral fat (all P ≤ 0.05). Compared with preintervention measures, the TRE group reduced the number of eating occasions (-21.9% [30.1%]) and reduced weight (-3.7% [1.8%]), fat mass (-4% [2.9%]), lean mass (-3.0% [2.7%]), and visceral fat (-11.1% [13.4%]) (all P ≤ 0.05). Physical activity and metabolic measures remained unchanged. CONCLUSIONS: In the setting of a randomized trial, TRE presents a simplified view of food intake that reduces weight.

Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis.

BACKGROUND: The relation between malnutrition and pulmonary death in patients with cystic fibrosis (CF) has resulted in intensive nutritional intervention over the last few decades, leading to a significant decline in underweight and the emergence of overweight/obesity as a potential new problem. METHODS: We performed a cross-sectional database analysis of 484 adults with CF seen at the University of Minnesota CF Center between January 2015-January 2017, to determine the prevalence and pulmonary/cardiovascular risk factors associated with overweight and obesity in this population. RESULTS: Mean age was 35.2 ±â€¯11.6 years. 5.2% were underweight (BMI<18.5 kg/m2), 62.6% normal weight (BMI ≥ 18.5-24.9 kg/m2), 25.6% overweight (BMI ≥ 25-29.9 kg/m2) and 6.6% obese (BMI ≥ 30 kg/m2). In the subgroup with severe genotypes, 25% had BMI ≥ 25 kg/m2. In the entire cohort, overweight/obese were likely to be older (OR = 1.04, p < 0.0001) and to have a mild CFTR genotype (OR = 3.33, p = 0.0003) and modestly elevated triglyceride levels (OR = 1.008, p < 0.0001). The prevalence of hypertension was higher in overweight (25%) and obese (31%) than normal (17%) or underweight (16%), p = 0.01. Total cholesterol levels were higher in overweight/obese versus normal/underweight (144-147 vs 123-131 mg/dL, p = 0.04) as were LDL levels (70-71 vs 53-60 mg/dL, p = 0.02), but all were within the normal range. Percent predicted FEV1 was higher in overweight/obese (78-81%) versus underweight (59%) and normal (70%), p < 0.0001, and overweight/obese experienced significantly fewer acute pulmonary exacerbations. CONCLUSIONS: Overweight/obesity is common in adults with CF including those with severe genotypes. Lung function is better in the overweight/obese and lipid levels are within the normal range, albeit higher than in normal/underweight.

Lumbar spine bone mineral density Z-score discrepancies by dual X-ray absorptiometry do not predict vertebral fractures in children.

Dual X-ray absorptiometry (DXA) remains the most common mode of bone mineral density (BMD) evaluation. In adults, presence of a lumbar spine (LS) BMD T-score discrepancy (>1 SD difference between adjacent vertebrae) can indicate a vertebral fracture. In children, however, the clinical significance of such discrepancies is unknown. We conducted a retrospective study to evaluate the association between LS DXA and LS morphology to elucidate the clinical significance of an LS BMD Z-score discrepancy. We identified 360 DXA scans performed between September 2014 and May 2016 in patients 5-18 years of age. DXA scans were cross-referenced against available LS radiographs and vertebral fracture assessment (VFA) within the 6 months preceding or following a DXA scan. After excluding 44 DXA scans because of spinal hardware, incomplete DXA, or repeat scans, 316 DXA scans were included; 81 (25.6%) had either an LS radiograph or a VFA. Twenty-five of 81 patients (30.9%) had >1 SD difference between adjacent vertebrae in LS BMD Z-score. Two of these 25 patients (8%) had a lumbar vertebral fracture documented by a spine radiograph. Of the remaining 56 patients who did not have a discrepancy >1 SD, 6 patients (11%) had a lumbar vertebral fracture. Discrepancies in LS BMD Z-scores were not associated with lumbar vertebral fractures and, in the absence of fractures, likely represented vertebral developmental variants in children whose skeletons are still growing. Therefore, it does not appear justified to recommend further imaging based solely on the results of a DXA scan without clinically meaningful indications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture. METHODS: The current meta-analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, Mantel-Haenszel analysis. RESULTS: A total of 20 studies with 8286 patients treated with SGLT2 inhibitors were included. The pooled risk ratio of bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95% confidence interval, 0.42-1.07). The pooled risk ratio for canagliflozin, dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37-1.19), 0.84 (95% confidence interval, 0.22-3.18), and 0.57 (95% confidence interval, 0.20-1.59), respectively. CONCLUSIONS: Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta-analysis. However, the results were limited by short duration of treatment/follow-up and low incidence of the event of interest.

Hypomagnesemia linked to new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis.

BACKGROUND: New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased mortality. The objective of this meta-analysis was to evaluate the risk of NODAT in patients with hypomagnesemia. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through May, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of NODAT in patients with hypomagnesemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Five cohort studies with 1699 patients were included in the analysis to assess the risk of NODAT in patients with hypomagnesemia. The pooled RR of NODAT in patients with hypomagnesemia was 1.25 (95% CI, 1.08-1.45). When meta-analysis was limited only to studies with the post-transplant hypomagnesemia, the pooled RR of NODAT was 1.22 (95% CI, 1.09-1.38). CONCLUSION: Our meta-analysis demonstrates a significant association between hypomagnesemia and NODAT in kidney transplant recipients. This finding suggests the need for a large randomized controlled trial-with very careful attention to assess the effects of normalizing Mg levels and the risk of NODAT.

Podocyte structural parameters do not predict progression to diabetic nephropathy in normoalbuminuric type 1 diabetic patients.

BACKGROUND: Podocyte injury has been implicated in diabetic nephropathy (DN) ranging from normoalbuminuria to proteinuria in both type 1 and type 2 diabetes. METHODS: To determine whether podocyte structural parameters predict DN risk in initially normoalbuminuric long-standing type 1 diabetic patients, we performed a nested case-control study in sex and diabetes duration-matched progressors (progression to proteinuria or ESRD, n = 10), non-progressors (normoalbuminuric at follow-up, n = 10), and non-diabetic controls (n = 10). RESULTS: HbA1c and diastolic blood pressure were higher in progressors versus non-progressors. Podocyte number per glomerulus, numerical density of podocyte per glomerulus, and foot process width were not different among groups. The glomerular basement membrane width was greater in progressors versus non-progressors or controls, and in non-progressors versus controls. As expected, the mesangial fractional volume was greater in progressors and non-progressors versus controls, with no differences between progressors and non-progressors. CONCLUSION: This study does not indicate that podocyte structural changes are preconditions for later DN progression in initially normoalbuminuric type 1 diabetic patients. However, this does not preclude an important role for podocyte injury at a later stage of DN.