scholarly journals Wolfram Syndrome: A Case Report and Review of Clinical Manifestations, Genetics Pathophysiology, and Potential Therapies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
N. B. Toppings ◽  
J. M. McMillan ◽  
P. Y. B. Au ◽  
O. Suchowersky ◽  
L. E. Donovan
Keyword(s):  
Diabetes Mellitus ◽  
Optic Atrophy ◽  
Cell Function ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Wolfram Syndrome ◽  
Biallelic Mutations ◽  
Therapeutic Considerations

Background.Classical Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations inWFS1,a gene implicated in endoplasmic reticulum (ER) and mitochondrial function. WS is characterized by insulin-requiring diabetes mellitus and optic atrophy. A constellation of other features contributes to the acronym DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). This review seeks to raise awareness of this rare form of diabetes so that individuals with WS are identified and provided with appropriate care.Case.We describe a woman without risk factors for gestational or type 2 diabetes who presented with gestational diabetes (GDM) at the age of 39 years during her first and only pregnancy. Although she had optic atrophy since the age of 10 years, WS was not considered as her diagnosis until she presented with GDM. Biallelic mutations inWFS1were identified, supporting a diagnosis of classical WS.Conclusions.The distinct natural history, complications, and differences in management reinforce the importance of distinguishing WS from other forms of diabetes. Recent advances in the genetics and pathophysiology of WS have led to promising new therapeutic considerations that may preserveβ-cell function and slow progressive neurological decline. Insight into the pathophysiology of WS may also inform strategies forβ-cell preservation for individuals with type 1 and 2 diabetes.

Tu-P10:422 Disregulated T-cell function and acute phase response in type 1 and type 2 diabetes mellitus

2006 ◽  
Vol 7 (3) ◽  
pp. 277
Author(s):  
S. Giubilato ◽  
S. Brugaletta ◽  
D. Pitocco ◽  
V. Colafrancesco ◽  
M. Narducci ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
T Cell ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Cell Function ◽  
Phase Response

scholarly journals Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 397
Author(s):  
Sangmi S. Park ◽  
Romy Rodriguez Ortega ◽  
Christina W. Agudelo ◽  
Jessica Perez Perez ◽  
Brais Perez Gandara ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Immune Mediated ◽  
Β Cell Function ◽  
Alpha 1 Antitrypsin

Alpha-1 antitrypsin (AAT) has established anti-inflammatory and immunomodulatory effects in chronic obstructive pulmonary disease but there is increasing evidence of its role in other inflammatory and immune-mediated conditions, like diabetes mellitus (DM). AAT activity is altered in both developing and established type 1 diabetes mellitus (T1DM) as well in established type 2 DM (T2DM). Augmentation therapy with AAT appears to favorably impact T1DM development in mice models and to affect β-cell function and inflammation in humans with T1DM. The role of AAT in T2DM is less clear, but AAT activity appears to be reduced in T2DM. This article reviews these associations and emerging therapeutic strategies using AAT to treat DM.

scholarly journals Predictors of Early Retinal Changes in Diabetes Mellitus

2020 ◽  
Vol 17 (1) ◽  
pp. 88-95
Author(s):  
V. S. Kulybysheva ◽  
I. A. Ronzina ◽  
A. A. Gamidov ◽  
V. G. Motalov ◽  
V. N. Nikolenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dynamic Control ◽  
Clinical Manifestations ◽  
Light Sensitivity ◽  
Control Group ◽  
Patients With Diabetes ◽  
Almost All

Purpose. Determining the functional state of the outer and inner retina’s layers in patients with diabetes mellitus (DM) type 1 and 2 before the clinical manifestations and in the early stages of diabetic retinopathy (DR) using the methods of multifocal electroretinography (mfERG) and microperimetry (MP).Patients and methods. 91 patients were examined (182 eyes). The patients were divided into 4 groups: 1st — 23 people (46 eyes) with diabetes without DR (the duration of the disease is up to 2 years); 2nd — 22 people (44 eyes) with diabetes without DR (diabetes from 2 to 8 years); 3rd — 24 people (48 eyes) with NPDR on the background of diabetes; 4th — 22 people (44 eyes) of the control group (healthy eyes). In addition to the standard ophthalmologic examination, all patients were registered mfERG (FOK1) on the diagnostic equipment EP-1000 Multifocal (Tomey, Germany) and carried out MP using the device “MAIA” (CenterVue, Italy).Results. According to mfERG, it has been established that the components of mfERG, the biopotential density and the amplitude of P1, are most sensitive to diabetic changes. In groups with type 1 and type 2 diabetes, there is a significant decrease in the density of P1 in comparison with the control group (p < 0.005, Mann-Whitney test), as well as a decrease in the amplitude of P1 on almost all tested rings (p < 0.005). In all groups, there is an increase in the latency of P1 in the central ring (0–2.3°). According to MP data, it was found that patients with type 1 and type 2 diabetes showed a decrease in the average light sensitivity in comparison with the control group, however, our data are within the reference values, regardless of the presence or absence of clinical manifestations of PD.Conclusion. As a result of the study, early functional and morphological disorders of the neurosensory apparatus of the eye in diabetes were identified. It is proved that mfER and MP allow to detect violations at the preclinical stage of DR and are necessary studies for the dynamic control of the progression of DR.

scholarly journals Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

2021 ◽  
Vol 22 (6) ◽  
pp. 3062
Author(s):  
Hideaki Kaneto ◽  
Atsushi Obata ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Tomoe Kinoshita ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Sglt2 Inhibitors ◽  
Protective Effects ◽  
Glucose Reabsorption ◽  
Β Cell Function ◽  
Glucose Lowering Effect ◽  
Glucose Excretion

Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass. Furthermore, it has been noted that SGLT2 inhibitors have cardio-protective and renal protective effects in addition to their glucose-lowering effect. In addition, several kinds of SGLT2 inhibitors are used in patients with type 1 diabetes mellitus as an adjuvant therapy to insulin. Taken together, SGLT2 inhibitors have amazing multifaceted effects that are far beyond prediction like some emerging magical medicine. Thereby, SGLT2 inhibitors are very promising as relatively new anti-diabetic drugs and are being paid attention in various aspects. It is noted, however, that SGLT2 inhibitors have several side effects such as urinary tract infection or genital infection. In addition, we should bear in mind the possibility of diabetic ketoacidosis, especially when we use SGLT2 inhibitors in patients with poor insulin secretory capacity.

scholarly journals The importance of multidisciplinary care of patients with Wolfram

2018 ◽  
Vol 1 (2) ◽  
pp. 01-03
Author(s):  
Rebecca A Dennison
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Insipidus ◽  
Optic Atrophy ◽  
Severe Hypoglycemia ◽  
Multidisciplinary Care ◽  
Wolfram Syndrome ◽  
Continuous Glucose Monitor ◽  
Hypoglycemia Unawareness ◽  
History Of

Background: Wolfram syndrome is a genetic condition, which is typically inherited in autosomal recessive fashion, characterized by the combination of diabetes mellitus and optic atrophy. It is along a spectrum which encompasses DIDMOAD (Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Profound hypoglycemic unawareness can be seen in this condition but is not commonly described as an associated feature in the literature. Case report: A 16 year old female with history of presumed type 1 diabetes presented to urology clinic with urinary incontinence. She was found to have profound dilation of the bladder and was admitted for bladder decompression. During the course of admission she was found to also have diabetes insipidus and optic atrophy. She had several severe hypoglycemic episodes with profound hypoglycemia unawareness during this admission. Genetic testing for Wolfram syndrome was positive. As an outpatient she was placed on a continuous glucose monitor to help manage her hypoglycemia. Addtionally, psychiatric support to manage her associated depression was an important aspect of her therapy. As her depression improved so did her ability to comply with the necessary therapies. Conclusions: Wolfram syndrome is a rare syndrome that has been well described. However, patients with this syndrome have frequent hypoglycemia unawareness and severe hypoglycemia likely related to the neurologic deterioration that occurs at the molecular level in the pathogenesis of Wolfram syndrome. Strategies must be put in to place to help prevent and quickly treat these hypoglycemic events.

scholarly journals PULMONARY TUBERCULOSIS WITH MULTIPLE DRAG-RESISTANT M. TUBERCULOSIS IN PATIENTS WITH DIABETES MELLITUS

2018 ◽  
Vol 24 (5) ◽  
pp. 254-257
Author(s):  
O. G Komissarova ◽  
Rizvan Yu.O. Abdullaev ◽  
S. V Aleshina ◽  
V. V Romanov
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Pulmonary Tuberculosis ◽  
Lung Tissue ◽  
Clinical Manifestations ◽  
Multidrug Resistant ◽  
Patients With Diabetes ◽  
Severe Intoxication

The aim of the study was to study the clinical manifestations and effectiveness of treatment of pulmonary tuberculosis with multidrug-resistant (MDR M. tuberculosis (MTB) in patients with different types of diabetes mellitus (DM). 66 patients with pulmonary tuberculosis combined with type 1 diabetes mellitus and 48 patients with pulmonary tuberculosis combined with type 2 diabetes were examined. It was found that in patients with type 1 DM, MDR tuberculosis was more often observed in men under 40 years of age, in the form of infiltrative pulmonary tuberculosis with the presence of destruction in lung tissue up to 2 cm in diameter with positive sputum and acute intoxication. In patients with type 2 DM, MDR tuberculosis was more often observed in men over the age of 40 in the form of fibrous-cavernous tuberculosis with the presence of destruction in lung tissue larger than 2 cm in diameter, with positive sputum and moderately severe intoxication. The effectiveness of treatment for negativation sputum in the compared groups did not differ significantly and amounted to 71,2% and 64,7%, respectively. However, to close the caverns in the lung, the treatment was more effective in patients with type 1 diabetes, which is probably due to the peculiarities of the tuberculosis process in this category of patients.

scholarly journals Evaluating the antidiabetic effects of R-verapamil in type 1 and type 2 diabetes mellitus mouse models

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255405
Author(s):  
Yu-Syuan Chen ◽  
Shao-Ju Weng ◽  
Shu-Hsien Chang ◽  
Rou-Ying Li ◽  
Guang-Tzuu Shane ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Side Effects ◽  
Cell Function ◽  
Serum Insulin ◽  
Β Cell ◽  
Type 2 Dm ◽  
Cardiovascular Side Effects ◽  
Β Cell Function

The global incidence of diabetes mellitus (DM) is increasing. Types 1 and 2 DM are associated with declining β-cell function. Verapamil (50% S-verapamil and 50% R-verapamil) can treat DM by downregulating thioredoxin-interacting protein (TXNIP), which induces islet β-cell apoptosis. However, it may also induce cardiovascular side effects as S-verapamil is negatively inotropic. In contrast, R-verapamil only weakly induces adverse cardiac effects. In this study, we aimed to determine the antidiabetic efficacy and cardiovascular safety of R-verapamil. We examined R- and S-verapamil binding through in vitro studies. Streptozotocin-induced type 1 and db/db type 2 DM mouse models were used to assess the antidiabetic efficacy of verapamil. IL-6, blood glucose (BG), Txnip expression, and β-cells were evaluated in streptozotocin-induced diabetic mice, while body weight, BG, and serum insulin were measured in the db/db mice. In the type 1 DM study, 100 mg/kg/day R-verapamil and racemic verapamil lowered BG, downregulated Txnip expression, and reduced β-cell apoptosis. In the type 2 DM study, the optimal R-verapamil dosage was 60 mg/kg/day and it lowered BG and raised serum insulin. However, efficacy did not increase with R-verapamil dosage. R-verapamil combined with metformin/acarbose improved BG and serum insulin more effectively than metformin/acarbose alone or verapamil combined with acarbose. R-verapamil had weaker cardiovascular side effects than S-verapamil. R-verapamil was 9.0× and 3.4× less effective than S-verapamil at inhibiting atrial inotropy and ileal contractility, respectively. It was also 8.7× weaker than S-verapamil as an agonist of somatostatin receptor type 2 (SSTR2), inhibiting ileal neurogenic contraction. Hence, R-verapamil may be an optimal DM treatment as it is safe, improves glycemic control, and preserves β-cell function both as monotherapy and in combination with metformin or acarbose. R-Verapamil has potential for delaying or arresting DM progression and improving patients’ quality of life.

scholarly journals Wolfram syndrome: a case report with severe polyuria and secondary urological abnormalities

2021 ◽  
Vol 8 (4) ◽  
pp. 759
Author(s):  
Niranjan kumbara Hunasagatta Omkarappa ◽  
Prashanth Siddaiah ◽  
Shalini Sankalapura Rangaswamy ◽  
Ramu Anjanaiah ◽  
Devika Chennakeshava ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Case Report ◽  
Diabetes Insipidus ◽  
Type 1 Diabetes Mellitus ◽  
Optic Atrophy ◽  
Sensorineural Deafness ◽  
Wolfram Syndrome ◽  
Dependent Diabetes Mellitus

Wolfram syndrome is the condition characterized by juvenile onset diabetes mellitus and optic atrophy, which is also known as DIDMOAD. Classical Wolfram syndrome is a rare autosomal recessive disorder caused by mutations in WFS1, a gene involved in endoplasmic reticulum and mitochondrial function. Patients present with type 1 diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts as early as in the third decade, and various neurological abnormalities in the early fourth decade. We describe a case report of 14-year-old male child diagnosed as wolfram syndrome with type 1 diabetes mellitus, diabetes insipidus, deafness, optic atrophy and severe urological abnormalities. Patients who present with early onset insulin-dependent diabetes mellitus and optic atrophy together should be evaluated with respect to Wolfram Syndrome. If a patient, who is a known case of diabetes mellitus, presents with persistent polyuria or neurogenic bladder despite good glycemic control, suspicion of wolfram syndrome and further evaluation regarding the same must be made. Recognizing and timely management of this condition will help to improve the quality of life in the patient.

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