Epidemiology and pathophysiological mechanisms involved in alteration of glomerular function in diabetic patients

Background: For a long time there has been a discussion about how chronic pancreatitis (CP) and diabetes mellitus (DM) are related to each other. If a patient has both conditions, should they be viewed as two separate disorders, or one of them is a plausible consequence of the other? If the latter is true, what are pathophysiological mechanisms of DM in CP? Current consensus documents by specialists in pancreatic diseases pay little attention to this issue, and their main statements have low level of evidence. The Russian consensus on the diagnosis and treatment of CP (2016) contains no statements on DM. In the Russian guidelines and consensus documents to be developed, it is necessary to include provisions on the pancreatogenic DM as an independent “other type DM’, with consideration of its pathophysiological mechanisms and clinical particulars.Aim: To characterize the state-of-the-art in pancreatogenic DM, to demonstrate its differences from DM types 1 and 2 from pathogenetic and clinical perspectives.Methods: The review is based on the results of meta-analyses, systematic reviews and main provisions of the existing clinical guidelines and consensus documents available from PubMed and E-library.Results: According to various sources, Type 3c DM, or latent impaired glucose tolerance in CP, can eventually develop in 25 to 80% patients with CP. Impaired glucose tolerance is found in 40 to 60% of patients with acute pancreatitis, with persistent hyperglycemia after acute episode seen in 15 to 18% of the patients. Exocrine pancreatic insufficiency is commonly seen in Type 1 and Type 2 diabetic patients, although the data on its prevalence are highly contradictory indicating a lack of knowledge in the field. Type 3c DM is characterized by its manifestation at later stages of CP, concomitant excretory deficiency of the pancreas, brittle course with proneness to hypoglycemia and no ketoacidosis. The highest risk group includes patients with longstanding CP, previous partial pancreatic resection and patients with early calcifying pancreatitis, mainly of the alcoholic origin. Optimal and rational medical treatment of pancreatogenic DM still remains disputable, while the evidence base of the efficacy and safety of various anti-diabetic agents in this disease is lacking, and no consensus on the issue has been yet reached. General treatment guidelines given in a number of international consensus documents are limited to cautious insulin administration.Conclusion: Pancreatogenic DM differs from Type 1 and Type 2 DM in a number of aspects, namely, mechanisms of hyperglycemia, hormonal profiles, clinical particulars and treatment approaches. Endocrine pancreatic insufficiency in CP is caused by secondary inflammatory injury of the pancreatic islets. The key to specifics of Type 3c DM lies in anatomical and physiological interplay of the exocrine and endocrine compartments of the pancreas. At presents, most provisions on pancreatogenic DM are empirical and seem to be rather declarative, because intrinsic mechanisms of this type of diabetes and moreover its pathogenetically based treatment have been poorly studied. Nevertheless, all patients with CP or other pancreatic diseases should be assessed for pancreatogenic DM.

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Pathophysiology of SARS-CoV-2 in Lung of Diabetic Patients

Frontiers in Physiology ◽

10.3389/fphys.2020.587013 ◽

2020 ◽

Vol 11 ◽

Author(s):

Tales Lyra Oliveira ◽

Igor Santana Melo ◽

Léia Cardoso-Sousa ◽

Igor Andrade Santos ◽

Mohamad Bassim El Zoghbi ◽

...

Keyword(s):

Glucose Metabolism ◽

Clinical Outcomes ◽

Research Progress ◽

Sufficient Evidence ◽

Diabetic Patients ◽

Type I ◽

Type Ii ◽

Pathophysiological Mechanisms ◽

Bacterial Proliferation ◽

Novel Coronavirus

Novel coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its impact on patients with comorbidities is clearly related to fatality cases, and diabetes has been linked to one of the most important causes of severity and mortality in SARS-CoV-2 infected patients. Substantial research progress has been made on COVID-19 therapeutics; however, effective treatments remain unsatisfactory. This unmet clinical need is robustly associated with the complexity of pathophysiological mechanisms described for COVID-19. Several key lung pathophysiological mechanisms promoted by SARS-CoV-2 have driven the response in normoglycemic and hyperglycemic subjects. There is sufficient evidence that glucose metabolism pathways in the lung are closely tied to bacterial proliferation, inflammation, oxidative stress, and pro-thrombotic responses, which lead to severe clinical outcomes. It is also likely that SARS-CoV-2 proliferation is affected by glucose metabolism of type I and type II cells. This review summarizes the current understanding of pathophysiology of SARS-CoV-2 in the lung of diabetic patients and highlights the changes in clinical outcomes of COVID-19 in normoglycemic and hyperglycemic conditions.

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Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ

Biochemical Journal ◽

10.1042/bj20100308 ◽

2010 ◽

Vol 432 (1) ◽

pp. 9-19 ◽

Cited By ~ 148

Author(s):

Balu K. Chacko ◽

Colin Reily ◽

Anup Srivastava ◽

Michelle S. Johnson ◽

Yaozu Ye ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Interstitial Fibrosis ◽

Immunohistochemical Analysis ◽

Cellular Damage ◽

Nuclear Accumulation ◽

Diabetic Patients ◽

Glomerular Function ◽

Mitochondrial Ros ◽

Akita Mice

Mitochondrial production of ROS (reactive oxygen species) is thought to be associated with the cellular damage resulting from chronic exposure to high glucose in long-term diabetic patients. We hypothesized that a mitochondria-targeted antioxidant would prevent kidney damage in the Ins2+/−AkitaJ mouse model (Akita mice) of Type 1 diabetes. To test this we orally administered a mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways were determined by immunohistochemical analysis, and mitochondria were isolated from the kidney for functional assessment. MitoQ treatment improved tubular and glomerular function in the Ins2+/−AkitaJ mice. MitoQ did not have a significant effect on plasma creatinine levels, but decreased urinary albumin levels to the same level as non-diabetic controls. Consistent with previous studies, renal mitochondrial function showed no significant change between any of the diabetic or wild-type groups. Importantly, interstitial fibrosis and glomerular damage were significantly reduced in the treated animals. The pro-fibrotic transcription factors phospho-Smad2/3 and β-catenin showed a nuclear accumulation in the Ins2+/−AkitaJ mice, which was prevented by MitoQ treatment. These results support the hypothesis that mitochondrially targeted therapies may be beneficial in the treatment of diabetic nephropathy. They also highlight a relatively unexplored aspect of mitochondrial ROS signalling in the control of fibrosis.

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Influence of exercise training on diabetic kidney disease: A brief physiological approach

Experimental Biology and Medicine ◽

10.1177/1535370220928986 ◽

2020 ◽

Vol 245 (13) ◽

pp. 1142-1154

Author(s):

Liliany Souza de Brito Amaral ◽

Cláudia Silva Souza ◽

Hernando Nascimento Lima ◽

Telma de Jesus Soares

Keyword(s):

Diabetes Mellitus ◽

Kidney Disease ◽

Exercise Training ◽

Diabetic Kidney Disease ◽

Negative Impact ◽

Experimental Models ◽

Diabetic Patients ◽

Diabetic Kidney ◽

Pathophysiological Mechanisms ◽

The Impact

Sedentary lifestyle is associated with increased incidence of diabetes mellitus, whereas exercise training improves metabolic control and therefore may contribute to prevention of various chronic complications. Diabetic kidney disease is the most common microvascular complication of diabetes mellitus, and is associated with increased mortality from cardiovascular disease in diabetic patients. The literature highlights oxidative stress, renal inflammation, and activation of the renin-angiotensin-aldosterone system as the main pathophysiological mechanisms underlying tissue damage, extracellular matrix accumulation, and renal function deficit. Unfortunately, although the benefits of exercise training on cardiovascular diseases are well established, their impact on the pathophysiological mechanisms involved in the development and progression of diabetic kidney disease is not well understood. In addition, standardization of experimental models and physical rehabilitation programs in diabetic kidney disease are scarce. In this article, we present a brief review of the pathogenesis and pathophysiological mechanisms of diabetic kidney disease,and bring to light the latest findings in the literature on the impact of exercise training on diabetic kidney disease progression. Impact statement Diabetic kidney disease (DKD) is associated with increased mortality in diabetic patients and has a negative impact on public health. The identification of potential therapies that help the management of DKD can contribute to the improvement of health and quality of life of patients. Thus, this paper is timely and relevant because, in addition to presenting a concise review of the pathogenesis and major pathophysiological mechanisms of DKD, it addresses the most recent findings on the impact of exercise training on this disease. Thus, since non-pharmacological interventions have gained increasing attention in the fight against chronic diseases, this paper appears as an important tool to increase knowledge and stimulate innovative research on the impact of exercise on kidney disease.

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Intramuscular Nerve and Neuromuscular Junction Alteration In Extraocular Muscles of Diabetic Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120102 ◽

1985 ◽

Vol 43 ◽

pp. 682-683

Author(s):

Bruce R. Pachter

Keyword(s):

Diabetes Mellitus ◽

Peripheral Nerves ◽

Sudden Onset ◽

Extraocular Muscles ◽

Diabetic Patients ◽

Oculomotor Palsy ◽

Third Nerve Palsy ◽

Patients With Diabetes ◽

Intramuscular Nerve ◽

Oculomotor Nerves

Diabetes mellitus is one of the commonest causes of neuropathy. Diabetic neuropathy is a heterogeneous group of neuropathic disorders to which patients with diabetes mellitus are susceptible; more than one kind of neuropathy can frequently occur in the same individual. Abnormalities are also known to occur in nearly every anatomic subdivision of the eye in diabetic patients. Oculomotor palsy appears to be common in diabetes mellitus for their occurrence in isolation to suggest diabetes. Nerves to the external ocular muscles are most commonly affected, particularly the oculomotor or third cranial nerve. The third nerve palsy of diabetes is characteristic, being of sudden onset, accompanied by orbital and retro-orbital pain, often associated with complete involvement of the external ocular muscles innervated by the nerve. While the human and experimental animal literature is replete with studies on the peripheral nerves in diabetes mellitus, there is but a paucity of reported studies dealing with the oculomotor nerves and their associated extraocular muscles (EOMs).

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A Comparison Between Sterological Point Counting and Digitizing Tablets

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120023 ◽

1985 ◽

Vol 43 ◽

pp. 666-667

Author(s):

John M. Basgen ◽

Eileen N. Ellis ◽

S. Michael Mauer ◽

Michael W. Steffes

Keyword(s):

Electron Microscopy ◽

Kidney Tissue ◽

Volume Density ◽

Diabetic Patients ◽

Normal Kidney ◽

Point Counting ◽

Normal Kidney Tissue ◽

Biopsy Specimens ◽

Mitochondrial Volume ◽

Kidney Lesions

To determine the efficiency of methods of quantitation of the volume density of components within kidney biopsies, techniques involving a semi-automatic digitizing tablet and stereological point counting were compared.Volume density (Vv) is a parameter reflecting the volume of a component to the volume that contains the component, e.g., the fraction of cell volume that is made up of mitochondrial volume. The units of Vv are μm3 /μm3.Kidney biopsies from 15 patients were used. Five were donor biopsies performed at the time of kidney transplantation (patients 1-5, TABLE 1) and were considered normal kidney tissue. The remaining biopsies were obtained from diabetic patients with a spectrum of diabetic kidney lesions. The biopsy specimens were fixed and embedded according to routine electron microscogy protocols. Three glomeruli from each patient were selected randomly for electron microscopy. An average of 12 unbiased and systematic micrographs were obtained from each glomerulus and printed at a final magnification of x18,000.

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