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Revista de medicina y complicaciones diabéticas

Volumen 5, Asunto 3 (2020)

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Diabetes 2018: Interferon-Based Antiviral Treatment of Chronic Hepatitis C in Combination with Metformin in Patients with HCV-1 Genotype and Insulin Resistance : Olga Tarasova - University of Russia (RUDN University)

Olga Tarasova

 

The efficacy of the antiviral therapy in patients with HCV genotype 1 infection rarely exceeds 40%.The main pre-treatment predictors of a sustained virological response (SVR) are: host genotype (in particular the CC genotype at the locus rs12979860 of the IL28B gene), viral genotype and pre-treatment viral load Other baseline factors providing a sustained response are: the right doses of Peginterferon (1.5 mcg/kg/week) and RBV (>10.6 mg/kg/ day), female gender, age less than 40 years, body weight (≤ 75 kg), elevated ALT (three-fold higher than upper limit of normal), the absence of bridging fibrosis or cirrhosis and the absence of insulin resistance (IR) [1-3]. Insulin resistance is the basic pathogenetic part of the metabolic syndrome. Obesity which is observed worldwide increases the number of patients with metabolic syndrome and hepatitis C. Also, it is assumed that HCV infection contributes to insulin resistance.IR caused by HCV together with insulin resistance as a result of metabolic syndrome, can accelerate the progression of disorders of carbohydrate metabolism leading to diabetes type II. Insulin resistance in hepatitis C, regardless of the pathogenesis leads to the development of steatohepatitis, promotes the progression of hepatic fibrosis, cirrhosis, and also reduces SVR rate during antiviral therapy for chronic hepatitis C. The most discussed drug, which can reduce IR, and may increase the SVR rate in patients with chronic hepatitis C- is metformin . Better insulin sensitivity may increase the response to antiviral treatment. The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-γagonists) have proved the efficacy of these drugs in patients with HCV [8]. Since November 2009 we have conducted a prospective study aimed to estimate the frequency of the SVR in 133 Russian patients with chronic hepatitis C (HCV-1), receiving standard therapy (PegIFNα-2b+ribavirin) in combination with metformin (in IR patients only). We studied IR using the method of "Homeostatic model» (Homeostasis Model Assessment). HOMA-index (HOMA-IR) is calculated based on the indices of insulin and glucose in one portion of serum: HOMA-IR = fasting insulin level (MkME/mL) x fasting glucose (mmol/L)/22.5. The criterion for the presence of IR value was decided to be HOMA-IR ≥ 2. All patients were assigned to the standard combination therapy PegIFN-α-2b (1.5 mcg/kg/ week) and ribavirin (15 mg/kg/day). 28 of 70 patients with chronic hepatitis C (HCV-1) and IR were given metformin (20 mg/kg/day). Liver fibrosis was measured with FibroScan®502 (Table 1).

                                                              

Results

133 patients were tested: 63 patients without IR and 70 patients with IR. 28 of 70 patients with IR received metformin. Metformin was prescribed at the start of antiviral treatment, or 3-6 months before the start of treatment and continued throughout the whole course of therapy. Patients in the second (control) group with IR did not receive metformin (n=42) (Table 2).

 

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Diabetes 2018: Risk Reduction Intervention to Reduce Risk of Type II Diabetes Mellitus at High Risk People in a Rural Area : Faculty of Nursing, Menoufia University

Naglaa E L Mokadem and Rehab Taman

Type II Diabetes Mellitus (DM) is a growing public-health burden worldwide, particularly in developing countries. Lifestyle modification can prevent or delay the onset of type II DM at high-risk adults. Most lifestyle intervention findings are driven from western studies which might not be appropriate for different cultures. Culturally sensitive interventions tailored to meet the specific needs of people in a rural area will facilitate the implementation and sustainability of behavior changes. The purpose of this study was to examine the effects of risk reduction intervention to reduce type II Diabetes Mellitus at high risk people in a rural area. A quasi experimental (Pre/post-test) design was used. A convenience sample of 70 patients with one or more risk factors of type II DM was recruited. This study was conducted at the outpatient clinics of Menoufia University Hospital at Shebein El- Kom City, Menofia Governorate, Egypt. Tools including: semi-structured demographic data sheet, The Australian Type II Diabetes Risk Assessment Tool and 24 Hours Dietary Recall Sheet. Culturally sensitive risk reduction intervention was tailored to meet the specific needs of at high risk people in the designated rural area. There was a statically significant difference in type II diabetes risk score pre and post intervention in the study group with a p value < 0.001. The lifestyle of people in developing country is different from industrialized developed countries, thus, developing preventive strategies to promote healthy lifestyles that are culturally appropriate and tailored for illiterate people with low socioeconomic status is crucial.

 

Results

Characteristics of the Sample

The mean age of the participants in the control group was 37.85 ± 10.94 years old and the mean age of the participants in the study group was 43.02 ± 10.81. The majority of participants (88.6%, 80%) were female in both control and study group respectively and most of them (80%) were married in both groups. Concerning the educational level of the participants in the study group 51.4% were secondary school and 51.43% in the control group were university graduates and the majority of participants were working 85.7%, 80% in both groups. As regard to the monthly income of participants 62.86%, 54.29% of participants in control and study group respectively were enough and this determined from the patient’s perception. See table 1.

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Diabetes 2018: Treatment of Diabetic Macular Edema with ILUVIEN (Fluocinolone Acetonide 0.19mg): Pharmacokinetics and Lipophilicity for the Primary Care Provider: Alyson Evans- Alimera Sciences

Alyson Evans

Diabetes mellitus is an epidemic worldwide. Primary care providers, including advanced practice registered nurses, can play a vital role in both the treatment of the disease and prevention of complications, particularly diabetic macular edemaA working comprehension of the ailment procedure and early referral is of excellent significance, as are long haul treatment choices patients may get from their ophthalmologist. ILUVIEN® (fluocinolone acetonide (FAc) intravitreal embed) 0.19 mg is an embed infused into the eye (glassy) and utilized for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant increase in intraocular pressure. The embed of ILUVIEN, a corticosteroid, gives a constant microdose of FAc for as long as three years. One must comprehend the pharmacokinetics of a medication as not all corticosteroids have a similar lipophilicity, water dissolvability and tissue penetration.as well as its lipophilic nature. The lipophilicity of FAc considers the ceaseless utilization of a microdose that is promptly retained into the retina, which clarifies why the FAc contiuous microdose can settle or improve vision for many patients, while reducing retinal edema. It is important for the primary care provider to appreciate the features of the drug and understand the implications of diabetic macular edema. Assertive, collaborative treatment is imperative for this patient population to maintain vision through their lifetime.

 

Diabetes as a National Epidemic It has been well documented that Type 2 diabetes mellitus (DM2) is a national epidemic in the United States. The Centers for Disease Control and Prevention estimated that in 2012, over 29 million people were diagnosed with DM2, and 1 in 4 people were undiagnosed. These statistics were even grimmer for those considered pre-diabetic: 86 million were prediabetic with 9 of 10 being unaware. Given these numbers, it is no surprise that primary care providers (PCPs) would see more patients with a myriad of complications, including those affecting vision. Diabetic macular edema (DME) is one of them; improved appreciation of this disease process and its treatments could enable PCPs to make a timelier referral, thereby positively affecting the patient’s vision over time, which when lost, may never be regained. Diabetic Macular Edema According to Bandello et al. DME, defined as “retinal thickening involving or approaching the center of the macula, represents the most common cause of vision loss in patients affected by diabetes mellitus.” DME is a multi-factorial disease process which includes multiple inflammatory cytokines and biochemical factors driven by local and systemic disease processes (Figure 1). For the PCP, management of the systemic disease is an important part of preventing ocular complications, but early referrals to ophalmologists and retina specialists are equally important. Understanding treatment options is critical, as some have systemic affect.

 

ILUVIEN (fluocinolone acetonide 0.19mg implant) as a Foundational Therapy for DME

 

ILUVIEN has been available in Europe since 2014 and in the US since 2015 (Figure 2). The US label indicates that it is for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. One trial of any ocular steroid, topical or intravitreal is sufficient to identify IOP hyper-responders. In the FAME study, ILUVIEN met the primary endpoint of proportion of patients with ≥ 15-letter improvement in BCVA from baseline at month 24 with sustained improvements through 36 months. The secondary endpoint of reduced retinal thickness was also met through 36 months. Class effect of cataract development and intraocular pressure elevation were the most common adverse events. Similar results were also seen in the USER study (Figure 3). Reduction in treatment frequency was also noted versus other options such as laser or anti angiogenic ocular injections Pharmacokinetics and Lipophilicity ILUVIEN is the novel treatment option as it combines a wellknown steroid with an innovative technology. The fluocinolone acetonide 0.19mg implant contains a lipophilic molecule which is encased in a semi-permeable, polymide shell approximately 3.5 mm long by 0.37 mm in diameter. It is implanted through as 25G needle into the eye and can last up to 36 months. This technology allows ILUVIEN to obtain near zero order pharmacokinetics and treat the retina with a continuous microdose of steroid. The continuous microdsoingin turn can result in decreased frequency of treatment over time as demonstrated in Figure 3.

 

Figure 1: Biochemical Factors and the Treatments that affect them in DME.

 

 

Figure 2: The ILUVIEN implant.

 

 

 

Figure 3: USER Study Visual Outcomes and Reduction in Treatment Frequency

 

Implications for the PCP

Vision is of critical importance to the PCP as it affects multiple areas of patients’ lives including:

• Visual-Motor Integration - Eye-hand/foot/body coordination.

• Visual-Auditory Integration - Associate what is seen and heard.

• Visual Memory - Remember and recall information that is seen.

• Visual Closure - Complete a visual picture based on seeing only some of the parts.

• Spatial Relationships - "Where I am" in relation to objects and space/where objects are in relation to one another.

• Figure-Ground Discrimination - Discern form and object from background. (Brainline.org).

 

The PCP plays an integral part in vision preservation. Systemic factors such as hypertension, glycemic control, renal impairment and lipid control can have a negative impact on long term vision, therefore appropriate management is important for vision protection. As previously discussed, prompt referral and long-term collaboration with local ophthalmologists and retina specialists is an important part in the continuum of care for the diabetic patient. Appreciation of the pathophysiology and treatment of DME, such as with ILUVIEN, can help enhance PCP competence in the care of the diabetic patient. Consultation between providers can help prevent untoward side effects of intravitreal and systemic medications due to a breached blood retinal barrier .

 

This work is partly presented at 2nd International Conference on Diabetes and Diabetic Nursing Care September during 28-29, 2018 at Montreal, Quebec, Canada

 

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Diabetes Asia Pacific 2017: Diabetes gastroenteropathy- Magdy El-Salhy- University of Bergen

Magdy El-Salhy

Introduction: Diabetic gastroenteropathy is a common complication in prolonged diabetic patients, especially patients with poor glycemic control or different difficulties, remembering all type of diabetic inconvenience for the gastrointestinal plot, which prompts different side effects of acid reflux, stomach torment, sickness, regurgitating, even stoppage, looseness of the bowels, and fecal incontinence. The basic pathophysiology of this difficulty signs are distinctive on every organ or indication, yet may incorporate autonomic sensory system neuropathy, loss of Interstitial Cell of Cajal as gastric muscle pacemaker prompting dysmotility, hinder of fluid transportation and motoric work, just as hyperglycemia causing oxidative pressure, and different elements like Insulin-Development Factor I inciting smooth muscle decay. Diabetic gastroenteropathy is one of significant grimness on diabetes mellitus patients.

 

Keywords: Complication; Diabetes Mellitus; Gastroenteropathy; Gastroparesis

 

Pathophysiological features and therapeutic considerations: All aspects of gastrointestinal motility have been implicated in the pathogenesis of diabetic gastroenteropathies. However, the correlation between individual symptoms and pathophysiologic changes is rather poor and there is high variability both between and within individuals.

 

Gastric dysfunction: Gastric symptoms and engine irregularities are normal in patients with both type 1 and type 2 diabetes. The motor abnormalities from the norm are heterogeneous and include both fast and delayed gastric emptying (gastroparesis), hindered fundic unwinding and ensuing strange intragastric dinner conveyance, diminished antral tone and motility, slow wave dysrhythmias, exceptional and delayed pyloric withdrawals ("pylorospasm") and impeded antropyloroduodenal coordination. Quickened gastric purging has most as often as possible been accounted for in "ahead of schedule" type 2 diabetes, i.e., in patients with generally brief span (<2 long periods) of the sickness and no proof of autonomic neuropathy. Distributed outcomes are conflicting as some depicted quick strong discharging while others discovered quickened discharging of liquids. Quick gastric exhausting isn't limited to type 2 diabetes. For instance, a subset of patients with long-standing sort 1 diabetes yet without gastrointestinal side effects was likewise found to have enormously quickened strong emptying. The hugeness of fast exhausting is that it might speak to a hazard factor for the improvement of hyperglycemia and helpless glucose control.30 from the human literature it isn't certain whether purging advances to typical fast or delayed emptying.

 

Symptoms in Several gastrointestinal patients with diabetes: Several gastrointestinal (GI) symptoms are common in patients with diabetes. These symptoms are refered to clinically as diabetes gastroenteropathy and incorporate queasiness and heaving, acid reflux, stomach torment loose bowels, obstruction and fecal incontinence. Diabetes gastroenteropathy not just diminishes significantly the personal satisfaction of diabetic patients, yet in addition debilitates metabolic control with increment danger of hyper-/hypoglycemia. The inadequately controlled blood glucose level increments thusly the danger of the optional diabetes confusions, for example, retinopathy, nephropathy, neuropathy and cardiovascular friendship. Diabetes gastroenteropathy may likewise cause lack of healthy sustenance, which along with the upset safe barrier in these patients may cause intercurrent contaminations. Diabetes gastroenteropathy is ascribed to gastrointestinal dysmotility, which is accepted to be brought about via autonomic neuropathy as well as hyperglycemia. The neuroendocrine system (NES) of the gut contains the gastrointestinal endocrine cells and the enteric nervous system. The neuroendocrine system of the gut secretes peptide/amines that manage the gastrointestinal motility through endocrine, paracrine as well as synaptic neurotransmission. The 2 components of the neuroendocrine system of the gut, specifically the gastrointestinal endocrine cells and the enteric nervous system has been seen as unusual in patients with diabetes and in creature models of human diabetes. The variations from the norm in the neuroendocrine system arrangement of the gut can clarify the gastrointestinal dysmotility found in patients with diabetes. The etiology of diabetes gastroenteropathy is by all accounts multifactorial, and autonomic neuropathy, hyperglycemia and strange gut neuroendocrine system seem, by all accounts, to be significant variables.

 

Discussion: Diabetic gastroenteropathy is a typical difficulty in delayed diabetic patients, especially patients with poor glycemic control or different entanglements, remembering all type of diabetic intricacy for the gastrointestinal lot, which prompts different side effects of acid reflux, stomach torment, queasiness, spewing, even clogging, the runs, and fecal incontinence. The hidden pathophysiology of this difficulty appearances are changed on every organ or manifestation, however may incorporate autonomic sensory system neuropathy, loss of Interstitial Cell of Cajal as gastric muscle pacemaker prompting dysmotility, disable of fluid transportation and motoric work, just as hyperglycemia causing oxidative pressure, and different elements like Insulin-Growth Factor I actuating smooth muscle decay. Diabetic gastroenteropathy is one of significant grimness on diabetes mellitus patients. Patients with this difficulty should be very much analyzed and precluded different finding prospects. The board of the complexity incorporates settling principle side effects and keeping up great glycemic control. With developing number of diabetes mellitus patients and the pervasiveness of diabetic gastroenteropathy complexity not being all around recorded, brought about by absence of consideration and information on social insurance supplier in recognizing the intricacy; it is imperative to have the option to distinguish and to give early treatment to diabetic gastroenteropathy patients, to build personal satisfaction and keep up glycemic control of the patient. Diabetic gastroparesis is one of most normal gastrointestinal entanglements of diabetes and is related with critical grimness. In past work, we discovered that signs of the illness are loss of heme oxygenase 1 (HOI), expanded reactive oxygen species (ROS) and ensuing loss of interstitial cells of Cajal (ICC). In fundamental examinations for this proposition, we have mentioned the accompanying key objective facts. Enlistment of HOI in the stomach happens basically in M2 macrophages in the stomach divider. Tissue from patients with diabetes without gastroparesis contains H01 communicating macrophages. HOI articulation is low in tissue from patients with diabetic gastroparesis. Expansion of cutting edge glycation end products (AGE) or reactive oxygen species to societies bring about loss of interstitial cells of Cajal. Acceptance of HOI turns around sub-atomic and electrophysiological changes related with postponed gastric purging. Tachygastria is available in diabetic mice with postponed gastric purging and is switched with hemin treatment.

 

This work is partly presented at 19th Asia Pacific Diabetes Conference on July 20-22, 2017 at Melbourne, Australia.

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Diabetes 2018: Analysis of Hypoglycemic Episodes in Diabetics in Africans Using Ademolus Classification of Hypoglycemia (ACH) : Adegbenga B Ademolu - Lagos State University Teaching Hospital

Adegbenga B Ademolu

 

Hypoglycemia as a management complication of diabetes mellitus is a world wide experience .Though concerted efforts have been made by endocrinologist, health workers and patients to reduce hypoglycemic episodes yet its occurrence and recurrence despite these efforts cannot be overemphasised. The glycemic thresholds for symptoms of hypoglycemia (among other responses) shift to lower plasma glucose concentrations after recent antecedent hypoglycemia  and to higher plasma glucose concentrations in patients with poorly controlled diabetes and infrequent hypoglycemia . Hypoglycemia in people living with diabetes mellitus in Africa is an uncharted territory in literature. To add to the existing knowledge in this area in Africa therefore, a number of questions will be addressed using Ademolus Classification of Hypoglycemia (ACH)Evaluation 1 has dominatingly adrenergic highlights, grade 2 has adrenergic highlights with neuroglycopenic include cover, grade 3 has prevalently neuroglycopenic highlights that are significantly reversible while grade 4 has overwhelmingly neuroglycopenic highlights with significantly irreversible cerebrum harm.

Hypoglycemia as an administration intricacy of diabetes mellitus (DM) is an overall encounter. In Africa, hypoglycemia is an unknown domain in writing. In this manner, the accompanying inquiries will be tended to utilizing Ademolus Classification of Hypoglycemia (ACH). Which is the commonest and the least regular evaluation of hypoglycemia in DM African patients? Which evaluation of hypoglycemia is seen ordinarily in type 1 and in type 2 diabetics?

Strategies: This is a review study that investigations 203 recorded hypoglycemic scenes in Africans with DM more than 9 years time frame. Utilizing a poll on 50 case documents contemplated. Hypoglycemia was characterized as a glucose of 70 mg/dl or less

Results:

It ought to be noticed that the examination is that of 203 recorded hypoglycemic scenes in 50 diabetics. The male to female proportion was 1:1.43 of the diabetics had type ll while 7 had type l DM. The age scope of the patients concentrated over the nine years 3 months time spans was 18 to 95 years, the age range among those with type l was 18-56years,while among the type ll it was 38-95years. The type 2 diabetics involved in this study had a total of 167 documented episodes of hypoglycemia while those with type l had 36 documented episodes. ln all these Africans, the average documented hypoglycemic episodes per patient was 4 episodes. Among the type 2 patients, the average hypoglycemic episodes is equally approximately 4 episodes per diabetics, while among the type l the average hypoglycaemic episodes are 5 per diabetic. The lowest documented hypoglycemia amongst type l diabetics in this study was 21mg/dl (grade 3 hypoglycemia) which was a nocturnal hypoglycemia that occurred at 1:00am while the lowest documented hypoglycemia amongst type 2 was 20mg/dl (grade 3 hypoglycemia) which was a fasting blood sugar documented at 6:00am.There was no record of grade 4 hypoglycemia in both type 1 and type2 diabetes mellitus patients in this African study. Now by using Ademolus Classification of Hypoglycemia to analyse the 203 hypoglycemic episodes,45.32% had grade 1 hypoglycemia,35.47% had grade 2 hypoglycemia while 19.21% had grade 3 hypoglycemia (Figure 1). With respect to the 167 episodes seen in type 2 diabetic, 48.50% had grade l hypoglycemia,35.93% had grade 2 hypoglycemia while 15.57% had grade 3 hypoglycemia (Figure 2).

 

 

A total of 127 hypoglycemic episodes were recorded in type 2 diabetes mellitus patients on insulin therapy alone. Of these 53.54% had grade 1 hypoglycemia, 31.50% had grade 2 hypoglycemia while 14.96% had grade 3 hypoglycemia (Figure 3).

 

The type 2 diabetics on both insulin and glucose lowering agents had 39 episodes of hypoglycemia recorded out of which 33.33% had grade 1 hypoglycemia,48.72% had grade 2 hypoglycemia while 17.95% had grade 3 hypoglycemia (Figure 4). Type 2 diabetics on glucose lowering agents alone could not be characterised by percentages of grade present as only one diabetic with one episode of hypoglycemia (grade 3) was involved in the study

 

The patients with type 1 diabetes mellitus had 36 hypoglycemic episodes, 30.50% of these were grade 1, 33.33% were grade 2 while 36.11% were grade 3 hypoglycemia (Figure 5).

 

 

There was no episode of grade 4 hypoglycemia in both type 1 and type 2 diabetes mellitus Africans patients involved in this study. By using the ADA/EASD 2018 classification of hypoglycemia, only 197 episodes of hypoglycemia met the classification definition of hypoglycemia as 6 episodes had 70mg/dl and did not qualified for hypoglycemia as defined by the ADA/EASD 2018 Classification of hypoglycemia as Analytically using ADA/EASD classification to analyse all the 197 hypoglycemic episodes studied, 77 (39.09%) hypoglycemic episodes had level 1 hypoglycemia, 90 (45.69%) had level 2 hypoglycemia while 30 (15.22%) had level 3 hypoglycemia.

Conclusions:

Grade 4 hypoglycemia was not recorded in both type 1 and type 2 diabetes mellitus in this African study. The commonest grade of hypoglycemia is grade 1 in type 2 and grade 3 in type 1 diabetics. The least common grade in type 2 diabetes is grade 3 while in type 1 it is grade 1. A similar study is recommended in Americans, Europeans, Asians and all ethnic groups for possibly racial differences or disparity in the findings of this research.

This work is partly presented at 2nd International Conference on Diabetes and Diabetic Nursing Care September during 28-29, 2018 at Montreal, Quebec, Canada

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