Diabetic Nephropathy: Present and Future Challenges
Meguid El Nahas in Kidney Diseases in the Developing World and Ethnic Minorities, 2005
An association between hyperglycemia and the development and progression of the microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy) has been suggested from several studies. Originally suggested by a study in 18 patients with type 1 diabetes by Nyberg and colleagues (50), the association between high levels of hemoglobin A1c (HbA1c) and diabetic nephropathy was confirmed in a number of studies involving a large number of patients (51,52). The association has been confirmed in the prospective Diabetes Control and Complications Trial (DCCT) (53), in which patients with type 1 diabetes were randomly assigned to receive either conventional therapy or intensive insulin therapy. The mean HbA1c values during the 9-year study were 7.2% with intensive therapy as opposed to 9.1% with conventional therapy. The study showed that strict glycemic control could both delay the onset of microvascular complications (primary prevention) and slow the rate of progression of already present complications (secondary intervention). Intensive insulin therapy is also effective at a somewhat later stage, after microalbuminuria develops (54).
Ameliorating Insulin Signalling Pathway by Phytotherapy
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in Ethnopharmacology of Wild Plants, 2021
Diabetes mellitus (DM) is an endocrine metabolic syndrome that is determined by elevated blood glucose level (hyperglycemia), poor secretion of insulin or miserable sensitivity of cells to the action of insulin (Fatemeh et al. 2017). Three clinical forms of diabetes have been recognized: type 1, type 2 and gestational diabetes. Type 1 diabetes, previously known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, is dominant in 5–10% of all diagnosed cases of diabetes (You and Henneberg 2016). Autoimmune disorders, environmental and genetic factors are known to be responsible for this form of diabetes. Type 2 diabetes was formerly known as non-insulin dependent diabetes mellitus (NIDDM) or adult-onset diabetes, which is the most common form prevailing in 90–95% of diabetic patients. NIDDM is directly linked with obesity, afflicted glucose tolerance, family history of diabetes, prior history of gestational diabetes, physical inactivity, cardiovascular diseases, hypertension and race/ethnicity (Vijan 2010). Among pregnant women, about 2–5% suffer from gestational diabetes mellitus (GDM) but in the most cases, GDM disappears following delivery (Eman 2015). To date, the exact cause of diabetes to a concerned person is unpredictable. Many reasons including specific hereditary disorders, drugs, malnutrition, surgery, infections, and different ailments are the principal culprit in developing diabetes (Singh and Singh 2008).
Hematopoietic Stem Cell Transplantation as Treatment for Type 1 Diabetes
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Diabetes is treated with either conventional insulin therapy or intensive insulin therapy (IIT). The goal of IIT is tight control of blood sugar. The risk of secondary complications (retinopathy, neuropathy, cardiovascular disease, nephropathy, extremity amputation, etc) from type 1 diabetes has changed over time and data on long term survival (i.e., 10, 20, and 25 years) using IIT is not yet available. For every 1% increase in HbAlc above normal (HgbAlc <6.5%), mortality increases 11%.31-34 With conventional insulin therapy, HgbAlc often remains between 9-12%. Since mortality in diabetes correlates with long term control of blood sugar, the current therapy for decreasing or delaying complications of diabetes is tight control of blood sugars using intensive insulin therapy.31-34 Intensive insulin therapy requires meticulous monitoring of blood sugar (4-10 times a day), frequent insulin injections (more than 3 times per day or an insulin pump), close control of diet, and is generally limited to motivated persons with regular access to health care. As quoted from the literature “Achieving optimal blood glucose control, without an unacceptable rate of hypoglycaemia or unacceptable restrictions on lifestyle, is not simple with presently available insulin preparations and monitoring tools. Accordingly, the appropriate use of insulin to obtain good metabolic control requires the continued and informed expertise of both patient and advising professional, but also attention from both to self-motivation in order to make the desired lifestyle changes possible”.35
Treatment strategies for hypertension in patients with type 1 diabetes
Published in Expert Opinion on Pharmacotherapy, 2020
Alexandra Katsimardou, Konstantinos Imprialos, Konstantinos Stavropoulos, Alexandros Sachinidis, Michalis Doumas, Vasilios G. Athyros
The Diabetes Control and Complications Trial (DCCT), a landmark clinical trial that examined the effects of intensive versus conventional insulin treatment in T1DM people, excluded hypertensive patients at randomization. Participants were frequently examined for the development of hypertension during the DCCT trial and its’ successor, the Epidemiology of Diabetes Intervention and Complications (EDIC) study. During a 15.8-year follow up period, 630 of 1441 participants, 96.5% of whom were white, developed hypertension. Although the incidence of hypertension was similar between the two study groups during the DCCT trial, participants that received intensive treatment had a reduction in the risk of incident hypertension by 24% during the EDIC study follow-up compared to those assigned to conventional treatment, highlighting the importance of glycemic control and metabolic memory in the development of hypertension in T1DM people. However, the benefits of intensive insulin treatment on the incidence of hypertension were partially mitigated by greater weight gain observed in this group. Older age, male sex, family history of hypertension, greater BMI and albuminuria were independently associated with the development of hypertension [21].
HbA1c method performance: The great success story of global standardization
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Emma English, Erna Lenters-Westra
The Diabetes Control and Complications Trial (DCCT) on people with type 1 diabetes mellitus, which was published in 1993, clearly demonstrated that the risk of the development and progression of microvascular complications was closely related to the degree of glycemic control [5]. Long-term follow-up studies show that macrovascular complications were also correlated with increasing HbA1c levels [6]. At the same time, as the DCCT study, the United Kingdom Prospective Diabetes Study (UKPDS) trial addressed improving glycemic control in patients with T2DM and similarly demonstrated that improved control, evidenced by lower HbA1c values, resulted in improved patient outcomes [7]. Since these studies were completed, numerous large-scale studies have added to our understanding of diabetes treatment and management, but HbA1c remains at the heart of new treatment regimens [8–16]. Treatments targets have moved away from those initially determined by early studies and are now based on multiple factors such as age of the person, duration of disease, co-morbidities, and likely compliance with therapy [17].
Pharmacological management of interstitial cystitis /bladder pain syndrome and the role cyclosporine and other immunomodulating drugs play
Published in Expert Review of Clinical Pharmacology, 2018
Teruyuki Ogawa, Osamu Ishizuka, Tomohiro Ueda, Pradeep Tyagi, Michael B. Chancellor, Naoki Yoshimura
Interstitial cystitis (IC) was initially reported by Hunner [1] as a rare type of bladder disease with ulcerative changes known as Hunner’s lesions [2]. The symptoms including urinary frequency and suprapelvic pain are often frustrating and difficult to treat. The leaky bladder urothelium has been considered as a pathophysiological basis of IC to impair the barrier function, resulting in bladder pain during filling; however, the mechanism inducing urothelial dysfunction is unclear. The diagnostic criteria have been changed for decades. In 1998, the National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) developed the strict criteria of IC, which was established mainly for clinical trials [3]. In 2011, the American Urological Association published the symptom-based definition and guideline [4], which defined IC/BPS as: the disorder with ‘an unpleasant sensation (pain, pressure and/or discomfort) associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes’, and indiscriminates the existence of Hunner’s lesion for the initial diagnosis [4].
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