Complications in Diabetes Mellitus Bench to Bedside with a focus on Bone Metabolism and Osteoporosis
An Academic Initiative by
Disclaimer: The views and opinions expressed in this publication are those of the authors based on his/her professional expertise and experiences and not of Lupin Limited.
Complications in Diabetes Mellitus Bench to Bedside with a focus on Bone Metabolism and Osteoporosis
Editor
Manoj Chadha MD DM (Endo)
Consultant Endocrinologist PD Hinduja Hospital Mumbai, Maharashtra, India
Foreword
Marc Evans
Jaypee Brothers Medical Publishers (P) Ltd.
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Complications in Diabetes Mellitus: Bench to Bedside with a focus on Bone Metabolism and Osteoporosis / Manoj Chadha
First Edition: 2023
9789354659423
Printed at:
This book is dedicated to my patients who have continued to trust me over the last three decades of my practice. Each patient is unique in their own way and has taught me something beyond Endocrinology.
Manoj Chadha
Editor
- Manoj Chadha MD DM (Endo)
- Consultant Endocrinologist
- PD Hinduja Hospital
- Mumbai, Maharashtra, India
Contributing Authors
- Abhinav Gupta MD (Internal Medicine), FRCP (Glasg, Edin)
- Senior Consultant Physician and Diabetologist
- Professor Medicine
- Acharya Shri Chander College of Medical Sciences and Hospital (Batra Hospital)
- Jammu, Jammu and Kashmir, India
- Aditya Panjabi MD
- Consultant Physician
- Morena, Madhya Pradesh, India
- Amit Kumar Diploma in Diabetology
- Diabetologist
- Patna, Bihar, India
- Animesh Choudhary MD
- Consultant Physician
- Narayana Hospital
- Raipur, Chhattisgarh, India
- Anuj Kumar Baruah MD (Medicine)
- Consultant Physician
- IIT Hospital
- Guwahati, Assam, India
- Arijit Samanta MD MRCP
- Diabetologist, Private Practice
- Midnapore, West Bengal, India
- Arunesh Singh MD
- Consultant Physician
- Bidla Hospital
- Satna, Madhya Pradesh, India
- Ashok Jangid MD
- Consultant Physician
- Mumbai, Maharashtra, India
- Banumathy Shrikant DNB
- Consultant Physician
- Mumbai, Maharashtra, India
- Bhabani Bhuyan MD
- Consultant Physician
- Times Hospital
- Tezpur, Assam, India
- Bharat Bhushan Kukreja MD (Medicine)
- Consultant Physician
- Guwahati, Assam, India
- Gautam Medhi MD
- Consultant Physician
- GD Hospital
- Nagaon, Assam, India
- Mridul Bera MRCP
- Diabetologist
- Private Practice
- Kolkata, West Bengal, India
- Mriganka Baruah MD
- Consultant Physician
- VG Hospital
- Dibrugarh, Assam, India
- Munim Rasul Mazumdar MD
- Nephrologist
- Mediland Hospital
- Silchar, Assam, India
- Neeraj Dayani MD
- Consultant Physician
- Geeta Bhawan Hospital
- Indore, Madhya Pradesh, India
- Noni Gopal Singha MD
- Consultant Physician
- Digboi, Assam, India
- Praveen Kumar Sinha MD
- Diabetologist
- Ranchi, Jharkhand, India
- Pritam Narkhedkar MD (Medicine)
- Consultant Physician
- Unique Hospital
- Solapur, Maharashtra, India
- Raj Kishore Agarwal MD
- Consultant Physician
- Mumbai, Maharashtra, India
- Santosh Tiwari MD
- Consultant Physician
- Mumbai, Maharashtra, India
- Smit Janrao MD (Medicine)
- Consultant Physician
- Newlife Hospital
- Solapur, Maharashtra, India
- Sunil Malla Bujar Barua MS MCh
- Endocrine and Breast Surgeon
- UHS Clinic
- Guwahati, Assam, India
- Supriya Datta MD
- Diabetologist, Private Practice
- Kolkata, West Bengal, India
- Vibhu Ranjan Khare MD (Medicine)
- DM (Endocrinology)
- Senior Resident
- Nil Ratan Sircar Medical College
- Kolkata, West Bengal, India
Diabetes is a growing global public health concern with patient numbers having quadrupled over the past three decades. It has been estimated that currently approximately 425 million adults (1 in 11) worldwide have diabetes, 90% of whom have type 2 diabetes mellitus (T2DM).
The disease burden in terms of both micro- and macrovascular complications in people with diabetes is well appreciated, with an ever increasing not only clinical but also economic considerations of such complications. Cognizant of such issues, coupled with the proliferation of cardiovascular outcome data extending into the mitigation of kidney disease and heart failure risk, international and national guidelines have evolved in such a way as to reflect the need for patient centricity and the choice of appropriate evidence-based therapies.
It is important to remember that diabetes has multiple other health considerations beyond vascular disease and one such area, which many clinicians may have lost sight of, is the effect of diabetes on bone health.
Kidney disease is a common complication of diabetes. It is estimated that up to 40% of people with diabetes will progress to developing chronic kidney disease, which through a variety of effects including perturbations of calcium and vitamin D metabolism will have detrimental effects on bone physiology.
However, both type 1 diabetes mellitus (T1DM) and T2DM affect bone metabolism at the cellular and biochemical levels, impacting upon normal bone homeostasis and microstructure. These effects in turn translate into an increased burden of a variety of bone pathologies in people with diabetes. T1DM and T2DM patients have a significant increase in the risk of osteoporosis and bone fracture, furthermore, fracture healing in people with diabetes is also impaired, which are all factors that can significantly contribute to the clinical, personal, and economic burden of diabetes care. Joint disorders are also more common in people with diabetes, some of which such as Charcot arthropathy may be a direct complication of diabetes, while in others diabetes may be a predisposing condition.
Another important consideration with respect to bone health in people with diabetes are the potential effects of commonly used diabetes therapies on bone physiology, bone health, density, and fracture risk.
With all these considerations in mind, bone and joint disorders clearly represent a significant burden of disease in people with diabetes. As such a detailed understanding of the effects of diabetes on bone health from the perspective of pathophysiology through to clinical manifestation and implications for therapy choices is essential to support optimal care of people with both T1DM and T2DM.
This book provides a thorough bench to bedside overview of the many aspects of bone and joint disorders in people with diabetes including the effects of diabetes on bone metabolism, the effects of diabetes on fracture and osteoporosis risk along with an overview of joint diseases, and future considerations in relation to diabetes and bone health.
This book therefore, serves to provide an invaluable source of reference material to shed light on an often-forgotten comorbidity of diabetes and consequently address a significant unmet need in the care of people with diabetes.
Marc Evans MD
Consultant Diabetologist
University Hospital Llandough
Cardiff, United Kingdom
PREFACE
With the pandemic of COVID-19 on the wane and moving toward an endemic stage, we have to again get back to our routine problems. We have been struggling for decades with diabetes mellitus and comorbidities. On the plus side, our understanding of the disease is increasing in leaps and bounds. At the same time, new drugs have been added to our armamentarium. They reduce HbA1c and provide end-organ protection. But, on the debit side, the number of cases of diabetes mellitus is increasing every year. These patients are surviving longer, thus increasing their chances of developing macrovascular and microvascular complications.
Osteoporosis is a serious and often neglected comorbidity of diabetes mellitus. Till very recently, it was missing from the list of complications of diabetes mellitus mentioned in textbooks. Now, we have recognized the risk of osteoporosis in diabetics. The etiology of increased bone fragility is different in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients. While the bone mineral density (BMD) is decreased in T1DM, T2DM patients have normal or even increased BMD. Most probably, the quality of bone is at fault in this set of patients.
The drugs used in the management of diabetes mellitus also affect bone and mineral metabolism. Thiazolidinediones in postmenopausal females definitely increase the risk of osteoporosis. Glucagon-like peptide receptor agonist (GLP-1 RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, on the other hand, have a positive outcome on the bone. Metformin and insulin have been shown to have variable effects in studies. Secretagogues are prone to causing hypoglycemia and hence increase the risk of falls and fractures.
There is some degree of confusion on the diagnostic criteria to be used for the diagnosis of osteoporosis in diabetic patients. A school of thought believes that a higher threshold of BMD should be used for diagnosis as they fracture at higher values of bone density. There is a suggestion to increase the diagnostic T value to −2.0. The FRAX (Fracture Risk Assessment Tool) score has no mention of diabetes mellitus while calculating the 10-year fracture risk. One suggestion has been to substitute RA with diabetes mellitus while calculating the fracture risk.
Bone turnover markers (BTM) in diabetics are being studied to understand the function of osteoclasts and osteoblasts. BTM should not be used for the diagnosis of osteoporosis. However, they are helpful in making a choice of therapy and in longitudinal follow-up of the patients.
All physicians should start thinking of diabetes mellitus as an important risk factor for osteoporosis. Preventive steps to reduce the risk of osteoporosis in diabetic patients should be taken as early as possible. The threshold for starting treatment against osteoporosis should be low. Management of osteoporosis would be the same as in nondiabetic patients.
I hope you find this book useful in your daily management of diabetic patients.
Manoj Chadha
ACKNOWLEDGMENTS
I acknowledge the effort of all the contributors for their support in completing this handbook. Each author has stuck to the timelines in submitting his/her chapters. The authors were open to discussion during the process of editing this handbook.
The staff at Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India were very prompt in helping with the corrections and queries that I kept sending them.
Last, but not the least, I acknowledge Dr Alka Chadha, who has been even a greater support than before (for the first two handbooks in this series). Her suggestions for editorial corrections of the chapters were always welcome.
Manoj Chadha