Zinc Insulin Research Articles

The Relationship between Levels of Zinc and Copper and Insulin Resistance in Polycystic Ovary Syndrome Patients in Homs

The Relationship between Levels of Zinc and Copper and Insulin Resistance in Polycystic Ovary Syndrome Patients in Homs

Evaluating insulindysregulation in horses: A two-step insulin-tolerance test using porcine zinc insulin

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT.

Marginal Zinc Deficiency Promotes Pancreatic Islet Enlargement While Zinc Supplementation Improves the Pancreatic Insulin Response in Zucker Diabetic Fatty Rats.

Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to β-cell exhaustion.

Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue.

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1mg/L) than subjects with overweight (87.0 ± 12.8mg/L) and obesity (83.1 ± 6.6mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r = - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

Serum Zinc Levels in Women with Polycystic Ovarian Syndrome are Lower as Compared to Those without Polycystic Ovarian Syndrome: A Cohort Study.

Zinc is an essential micronutrient, a vital stabiliser and a cofactor in many enzymes such as superoxide dismutase and phospholipase C and also acts as an antioxidant by protecting the sulfhydryl groups of different proteins and enzymes against free radicals. It is unclear if serum zinc levels are correlated with polycystic ovary syndrome (PCOS) and its pathophysiology, although relation between diabetes and insulin resistance has been established. This study aimed to investigate circulating serum zinc levels in PCOS subjects compared with non-PCOS subjects. In this cohort study, PCOS subjects were compared with normal subjects aged between 18 and 35. All the included subjects underwent measurement of anthropometric parameters, fasting insulin, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, progesterone, oestrogen and serum zinc levels. These values were taken on days 2-5 of the menstrual cycle. Univariate analysis and linear regression were performed for serum zinc levels and fasting insulin levels in PCOS subjects and non-PCOS subjects using SPSS (version 21) and Microsoft Excel (2019). Serum zinc levels in the PCOS group were lower than in the control group (P = 0.012). Fasting insulin levels in the PCOS group were higher than in non-PCOS subjects (P = 0.001). We found a negative correlation between zinc and fasting insulin (r = -0.580, P < 0.0001) in the normal group and (r = -0.332, P = 0.019) in the PCOS group. A positive correlation was found between body mass index (BMI) and fasting insulin levels in both the PCOS group (r = 0.227, P = 0.112) and normals (r = 0.612, P < 0.0001). A negative statistically significant correlation between BMI and zinc in both the PCOS group (r = -0.378, P = 0.007) and the non-PCOS group (r = -0.7452, P < 0.0001) was seen. The data suggest that serum zinc levels were found to be lower in PCOS subjects as compared to normal controls and evaluation of these levels may indicate that zinc has a vital role in PCOS pathophysiology.

Single-molecule analysis of intracellular insulin granule behavior and its application to analyzing cytoskeletal dependence and pathophysiological implications.

Introduction: Mobilization of intracellular insulin granules to the plasma membrane plays a crucial role in regulating insulin secretion. However, the regulatory mechanisms of this mobilization process have been poorly understood due to technical limitations. In this study, we propose a convenient approach for assessing intracellular insulin granule behavior based on single-molecule analysis of insulin granule membrane proteins labeled with Quantum dot fluorescent nanocrystals. Methods: This approach allows us to analyze intracellular insulin granule movement with subpixel accuracy at 33 fps. We tracked two insulin granule membrane proteins, phogrin and zinc transporter 8, fused to HaloTag in rat insulinoma INS-1 cells and, by evaluating the tracks with mean-square displacement, demonstrated the characteristic behavior of insulin granules. Results and discussion: Pharmacological perturbations of microtubules and F-actin affected insulin granule behavior on distinct modalities. Specifically, microtubule dynamics and F-actin positively and negatively regulate insulin granule behavior, respectively, presumably by modulating each different behavioral mode. Furthermore, we observed impaired insulin granule behavior and cytoskeletal architecture under chronic treatment of high concentrations of glucose and palmitate. Our approach provides detailed information regarding intracellular insulin granule mobilization and its pathophysiological implications. This study sheds new light on the regulatory mechanisms of intracellular insulin granule mobilization and has important implications for understanding the pathogenesis of diabetes.

Absence of Slc39a14/Zip14 in mouse pancreatic beta cells results in hyperinsulinemia.

Zinc is an essential component of the insulin protein complex synthesized in β cells. The intracellular compartmentalization and distribution of zinc are controlled by 24 transmembrane zinc transporters belonging to the ZnT or Zrt/Irt-like protein (ZIP) family. Downregulation of SLC39A14/ZIP14 has been reported in pancreatic islets of patients with type 2 diabetes (T2D) as well as mouse models of high-fat diet (HFD)- or db/db-induced obesity. Our previous studies observed mild hyperinsulinemia in mice with whole body knockout of Slc39a14 (Zip14 KO). Based on our current secondary data analysis from an integrative single-cell RNA-seq dataset of human whole pancreatic tissue, SLC39A14 (coding ZIP14) is the only other zinc transporter expressed abundantly in human β cells besides well-known zinc transporter SLC30A8 (coding ZnT8). In the present work, using pancreatic β cell-specific knockout of Slc39a14 (β-Zip14 KO), we investigated the role of SLC39A14/ZIP14-mediated intracellular zinc trafficking in glucose-stimulated insulin secretion and subsequent metabolic responses. Glucose-stimulated insulin secretion, zinc concentrations, and cellular localization of ZIP14 were assessed using in vivo, ex vivo, and in vitro assays using β-Zip14 KO, isolated islets, and murine cell line MIN6. Metabolic evaluations were done on both chow- and HFD-fed mice using time-domain nuclear magnetic resonance and a comprehensive laboratory animal monitoring system. ZIP14 localizes on the endoplasmic reticulum regulating intracellular zinc trafficking in β cells and serves as a negative regulator of glucose-stimulated insulin secretion. Deletion of Zip14 resulted in greater glucose-stimulated insulin secretion, increased energy expenditure, and shifted energy metabolism toward fatty acid utilization. HFD caused β-Zip14 KO mice to develop greater islet hyperplasia, compensatory hyperinsulinemia, and mild insulin resistance and hyperglycemia. This study provided new insights into the contribution of metal transporter ZIP14-mediated intracellular zinc trafficking in glucose-stimulated insulin secretion and subsequent metabolic responses.NEW & NOTEWORTHY Metal transporter SLC39A14/ZIP14 is downregulated in pancreatic islets of patients with T2D and mouse models of HFD- or db/db-induced obesity. However, the function of ZIP14-mediated intracellular zinc trafficking in β cells is unknown. Our analyses revealed that SLC39A14 is the only Zn transporter expressed abundantly in human β cells besides SLC30A8. Within the β cells, ZIP14 is localized on the endoplasmic reticulum and serves as a negative regulator of insulin secretion, providing a potential therapeutic target for T2D.

Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

THU358 A Case Of Latent Autoimmune Diabetes In Adults (LADA) Managed By Lifestyle And Dietary Intervention Alone

Abstract Disclosure: M. Ahmad: None. U. Tarabichi: None. R. Patel: None. B. Arshad: None. A.P. Calimag: None. Introduction: LADA typically presents like Type 2 Diabetes at the time of diagnosis but it slowly progresses to insulin dependence for management. LADA is an autoimmune disease and it is distinguished from Type 2 diabetes by the presence of autoantibody. We present you an interesting case in which patient was diagnosed with LADA and was started on treatment with insulin regimen but over the time patient managed to stay off of insulin and managing his condition exclusively with a high protein ketogenic diet. Case Description: A 57 year old male with past medical history of Hyperlipidemia, gastroparesis, Hypertension and Diabetes. Patient initially diagnosed with diabetes in 2016 with A1C of 11% and was started on Metformin. In 2017, patient was admitted with diabetic ketoacidosis (DKA), had low c peptide on admission. At discharge, patient was started on basal bolus regimen. Patient had a follow up with Endocrinology and autoimmune labs. These were positive for GAD antibody, islet cell antibody and low c-peptide. With subsequent follow ups, lantus dose was decreased and Humalog with meals was discontinued. On further questioning patient reported that he started ketogenic diet along with intermittent fasting in March 2020. With his change of diet, he lost around 100 pounds over 1 year period and his insulin requirements continued to decrease throughout his journey. With time, patient desired to be off of insulin but Endocrinology didn’t recommend given his increased risk of DKA. Patient eventually stopped taking all of his insulin and it was recommended that he continues to use continuous glucose monitoring along with keto testing strips at home to monitor for DKA. Patient has sustained his diet change until this date and he continues to be on ketogenic diet with intermittent fasting 20 hours a day with 4-hour window of eating. He remains off insulin for 2 years, A1C continues to trend down, and with no evidence of DKA. Most recent labs; A1C is 5.5, positive for insulinoma associated antibody 2, negative for Zinc transporter antibody and insulin antibody. Conclusion: There is very little evidence available in the literature that supports treatment of LADA with dietary intervention alone. In our case, there are several fasting cpeptide levels that are less than 1.0, which typically would indicate initiation of insulin therapy. Our patient has managed to control hyperglycemia with dietary changes alone and has not been in diabetic ketoacidosis for greater than 2 years. It is rare for someone to maintain such a restrictive diet which includes 100g of protein, 100g fat and 5g of carbohydrates per day. This case highlights the ability of someone to maintain euglycemia with LADA without need for insulin therapy for greater than 2 years. Most diet studies are not followed that Longterm. Presentation: Thursday, June 15, 2023

Refrigerated multi-dose insulin vials remain sterile through 6 months of use.

To evaluate sterility in refrigerated multi-dose insulin vials through 6 months of routine aspiration. Twelve vials of insulin, six of insulin glargine U100 (Lantus®, 10 mL multi-dose vial, Sanofi, Bridgewater, NJ) containing the preservative metacresol, and six of protamine zinc insulin U40 (ProZinc®, 10 mL multi-dose vial, Boehringer Ingelheim, Duluth, GA) containing the preservative phenol, were refrigerated and aspirated twice daily for 6 months, using a new insulin syringe each time. Three vials of each insulin type were wiped with a single-use alcohol swab before sampling. Three times weekly, aspirated samples were inoculated in Tryptic Soy Broth enrichment media and incubated for evidence of microbial growth. Positive broth was cultured and speciated. Endpoints were microbial vial contamination (defined as three consecutive positive cultures of the same organism) and completion of the six-month study period. Microbial contamination was not identified in any vial throughout the study period. A total of 454 aspirated samples were cultured, one of which exhibited non-repeatable growth of Staphylococcus epidermidis. This vial was prematurely lost to breakage after 59 culture samples (29 after the positive growth). Refrigerated phenol- and metacresol-containing multi-dose insulin products carry minimal risk for iatrogenic infection through 6 months of use, regardless of alcohol swab preparation.

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses

Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover study. Serum insulin concentrations during the OGT revealed that six horses were hyperinsulinemic (HI) while six were not (NON-HI). To describe the glucose response to IV injected PZI, the decline of plasma glucose concentration within the first 30 min was analyzed. Glucose reduction was similar in horses with and without HI during the 2-step IRT over time. Additionally, none of the horses reached a glucose reduction of ≥ 50% at 30 min. The results of the present study indicated that a comparable insulin mediated glucose uptake may be observed in horses with and without HI during a modified 2-step IRT. While six out of twelve horses were identified as HI by the OGT, all twelve horses were identified as IR by the modified 2-step IRT performed with PZI underlining the importance, but difficulty in choosing the right diagnostic tool in clinical settings to assess ID.

Insulin icodec: evolution or revolution in diabetes therapy?

The isolation of insulin in 1922 was hailed as a miracle of medical science, life-saving for thousands and health-preserving for many more. 1 Bliss M The discovery of insulin. 6th edn. University of Chicago Press, Chicago, IL1984 Google Scholar Efforts to develop longer-acting formulations, to allow for more sustained glycaemic control and improve treatment satisfaction, started in the 1930s with initially the development of protamine (NPH) and zinc (lente) insulins. 2 Vecchio I Tornali C Bragazzi NL Martini M The discovery of insulin: an important milestone in the history of medicine. Front Endocrinol (Lausanne). 2018; 9: 613 Crossref PubMed Scopus (103) Google Scholar Subsequent decades saw the sequencing of the insulin molecule and a better understanding of its structure and action. 2 Vecchio I Tornali C Bragazzi NL Martini M The discovery of insulin: an important milestone in the history of medicine. Front Endocrinol (Lausanne). 2018; 9: 613 Crossref PubMed Scopus (103) Google Scholar Further research led to the development of human and analogue insulins. These incremental advances allowed greater flexibility in insulin administration and the potential to tailor insulin regimens that more closely mimic normal physiology. Despite these developments, however, achieving sustained glycaemic control while avoiding hypoglycaemia and weight gain together with preserving quality of life and treatment satisfaction remains a considerable challenge. 3 Sorli C Heile MK Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J Multidiscip Healthc. 2014; 7: 267-282 Crossref PubMed Scopus (55) Google Scholar The search for molecules with better pharmacodynamic profiles has therefore continued and has led to an expanding list of so-called designer insulins. One such formulation is insulin icodec, with a half-life of 196 h, suitable for once-weekly administration. 4 Nishimura E Pridal L Glendorf T et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. 2021; 9e002301 Crossref Scopus (20) Google Scholar Its ultra-long-acting profile relates to a combination of lower affinity for the human insulin receptor and strong, but reversible, binding to human serum albumin. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trialAmong adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbA1c reduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. Full-Text PDF

Diabetes mellitus in dachshund dogs: A case report of three dogs

Diabetes mellitus is an endocrinopathy associated with insulin insufficiency or insulin resistance. Three female middle-aged Dachshund dogs presented with clinical signs of polyuria, polydipsia, cataract and emaciation were diagnosed with diabetes mellitus using portable blood glucose monitor. One of the dogs succumbed with diabetic ketoacidosis (ketone bodies of 7.4 mmol/L) with concomitant diabetic nephropathy and hypercalcemia. Leukocytosis, elevated liver enzymes, cholesterol and glycosuria were evident in all the dogs. Blood glucose level was effectively managed with human recombinant DNA protamine zinc insulin administration twice daily for a period of six months.

Owner preference for insulin delivery device and glycaemic control in diabetic dogs.

To assess treatment satisfaction and owner preference for two delivery devices (VetPen, MSD Animal Health, and U40 insulin syringes) and the effect on glycaemic control in diabetic dogs treated with porcine insulin zinc suspension. Randomised prospective cross-over study with two arms, each of 8 weeks. Twenty client-owned diabetic dogs on insulin treatment by U40 syringe were enrolled. Dogs were randomly assigned to receive insulin by syringe or pen injector for 2 months, followed by 2 months of the other injection method. Treatment satisfaction and owners' insulin delivery device preference were assessed using a questionnaire. Glycaemic control was assessed using a clinical score, serum fructosamine and glycated haemoglobin (HbA1c%) at the time of the enrolment (T0) and the end of each arm of treatment (T2 and T4). Treatment satisfaction differed for the two types of the delivery device when the order that each device was used was taken into consideration. Owners who used the syringe first did not have a significant preference for an injection device. In contrast, owners who used the pen injector first expressed a significant preference for VetPen compared to syringes. No significant differences in the number of dogs of Groups 1 and 2 with good and poor glycaemic control at T2 and T4 were detected. Overall treatment satisfaction and preference for the two delivery methods were similar. However, VetPen was preferred by owners who were randomised to use this device first. Glycaemic control did not appear to be affected by the insulin delivery device used.

Zinc insulin hexamer loaded alginate zinc hydrogel: Preparation, characterization and in vivo hypoglycemic ability

Alginate zinc hydrogel loaded with zinc insulin hexamer was prepared and characterized for oral insulin administration. The hydrogel was fabricated by dripping zinc insulin hexamer into sodium alginate solution and followed by crosslinking by zinc chloride. SEM image reveals the zinc insulin hexamer was integrated into the matrix of hydrogel. Zinc insulin hexamer loaded hydrogel shows no obvious cytotoxicity to both HT29 and Caco-2 cells. The developed hydrogel retards the burst release of insulin in simulated gastric fluid but promotes the release when in simulated intestinal fluid. In the diabetic mice, zinc insulin hexamer loaded alginate hydrogel demonstrates significant and prolonged hypoglycemic effect.

One hundred years of insulin: Is it time for smart?

Smarter understanding of diabetes pathophysiology and pharmacology of insulin therapy can lead to better clinical outcomes. Rather than looking for an insulin formulation that is considered "best" for a general population, it could be appropriate to seek the "smart" insulin choice, tailored to the specific clinical situation. Different treatment goals should be considered, with pros and cons to each. Ideally, insulin therapy in most diabetic dogs should mimic a "basal-bolus" pattern. The "intermediate"-acting insulin formulations might provide better "bolus" treatment in dogs than the rapid-acting formulations used in people. In patients with some residual beta cell function such as many diabetic cats, administering only a "basal" insulin might lead to complete normalisation of blood glucose concentrations. Insulin suspensions (neutral protamine Hagedorn, neutral protamine Hagedorn/regular mixes, lente and protamine zinc insulin) as well as insulin glargine U100 and detemir are "intermediate"-acting formulations that are administered twice daily. For a formulation to be an effective and safe "basal" insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.

Zinc status, insulin resistance and glycoxidative stress in elderly subjects with type 2 diabetes mellitus.

Zinc deficiencies have been reported in numerous pathologies, such as diabetes mellitus, but also in the physiological process of ageing. Similarly, the end products of glycoxidation processes, advanced glycation end products (AGEs), are damaging compounds, a myriad of reports linking them to the development and progression of several age-associated chronic diseases. The aim of the present study was to analyze the relationships between zinc status, glycoxidative stress and insulin resistance (IR) in elderly subjects with type 2 diabetes mellitus (T2DM). A group of 52 non-smoking subjects (9 men and 43 women, aged 65-83 years) were enrolled in this cross-sectional study: 27 patients with T2DM, and 25 apparently healthy control subjects. Serum zinc (Zn) levels were assessed using a commercial kit based on an end-point colorimetric method, and serum AGEs were evaluated with a fluorimetric analytic procedure. The calculated glucose-to-zinc ratio (Gly/Zn), insulin-to-zinc ratio (Ins/Zn) and insulin-zinc resistance index (HOMA-IR/Zn) were further used to study the associations between serum Zn levels, secretory function of β-pancreatic cells and AGEs. T2DM patients presented significantly higher serum insulin and Zn levels, as compared to the controls. We found a significant inverse correlation between Zn and AGEs, and a strong positive correlation between AGEs and the Gly/Zn ratio, suggesting that both Zn and AGEs are biomarkers that could reflect the persistence of hyperglycemia. We identified new surrogate biomarkers useful for the assessment of glycemic control with great potential for the development of preventive and therapeutic strategies for elderly diabetics, based on the evaluation of serum Zn levels.

Disease Prevention through Lifestyle: A Case of the Copper to Zinc Ratio and Insulin Sensitivity

Both type 2 diabetes mellitus and a high ratio of copper to zinc are independently associated with comorbidities involving multiple organs. Separately, patients with poor insulin sensitivity are often reported as having high copper and low zinc. This article reports the case of a 46-year-old male patient interested in reversing his insulin resistance and high copper to zinc ratio, therefore reducing his long-term risk of Alzheimer’s disease. Over a period of 16 weeks, through lifestyle changes and controlling for copper in the patient’s food and water supply, the patient’s copper to zinc ratio improved from 1.91 to a healthy level of 0.55 and his HOMA-IR score improved from 2.0 to a nondiabetic level of 1.2.

Insulin choice in feline diabetes mellitus

PICO question&#x0D; In cats with diabetes mellitus, do protamine zinc insulin (PZI) and glargine show a similar effect in reducing clinical signs and hypoglycaemia episodes?&#x0D; &#x0D; Clinical bottom line&#x0D; Category of research question&#x0D; Treatment&#x0D; The number and type of study designs reviewed&#x0D; The number and type of study designs that were critically appraised was one. This study was a non-randomised retrospective trial. A systematic review was also found, which analyses the influence of insulin in diabetic remission&#x0D; Strength of evidence&#x0D; Weak&#x0D; Outcomes reported&#x0D; Compared to PZI, using glargine in recently diagnosed diabetic cats fed exclusively an ultra-low carbohydrate-high protein canned diet, may result in lower fructosamine and mean 12 hour blood glucose concentrations as well as less episodes of hypoglycaemia&#x0D; Conclusion&#x0D; In view of the strength of evidence and the outcomes from the study the following conclusion is made: in cats with diabetes mellitus where currently licensed insulin fails to result in a good glycaemic control, glargine may be considered&#x0D; &#x0D; How to apply this evidence in practice&#x0D; The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.&#x0D; Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.&#x0D; &#x0D;

Pharmacological Management of Diabetes Mellitus: A Century of Expert Opinions in Cecil Textbook of Medicine.

Drug therapy for diabetes mellitus (DM) has had a significant impact on quality of life and work potential of affected persons and has contributed to a remarkable decrease in the frequency and severity of complications, hospitalizations, and mortality. The current approach is the result of incremental progress in using technological advances to increase the safety and effectiveness of insulin therapy and the introduction of new molecules as oral and injectable antidiabetic drugs. What are the milestones of the changes in the expert approach to the pharmacological management of DM in the past century? To determine the changes in the experts' approach to the management of DM, as presented in a widely used textbook in the United States. The chapters on describing the management of DM in the 26 editions of Cecil Textbook of Medicine published from 1927 to 2020. In 1927, DM was treated with insulin extracted from the pancreas of large animals (cattle, hogs, and sheep) and purified with alcohol to prevent the tissues' proteolytic action on the hormone. The therapeutic milestones in DM marked 2 avenues for innovation. The first created advances in insulin therapy, starting with processes that led to the production of crystalline insulin and protamine zinc insulin (1937), synthetic human insulin (1996), and prandial (2000) and basal (2004) insulin analogues. The second was an effort to develop and introduce in clinical practice in the United States oral antidiabetic drugs, starting with tolbutamide, a sulfonylurea (1955), followed by metformin, a biguanide (1996), thiazolidinediones, alpha-glucosidase inhibitors, and benzoic acid derivatives (2000), dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists (2008), and sodium glucose cotransporter 2 inhibitors (2020). A latent period of 40 years between significant advances was likely because of searches for new technologies (eg, recombinant DNA for the production of synthetic insulin and analogues) and, at least in part, to the impact of the controversial University Group Diabetes Project on the development and acceptance of oral antidiabetic drugs. The pharmacological management of DM has progressed unevenly, with a long latency period in the second half of the last century followed by highly encouraging advances in the first 2 decades of the 21st century. In chronological order, the major advances were synthetic insulins obtained through DNA recombinant technology, adoption of metformin as first line therapy, and introduction of antidiabetic medication classes that also promote weight reduction and cardiovascular health.