Drug induced Dysglycemia
ā¢
2 likesā¢476 views
Drug induced Dysglycemia Presented by Usama Ragab Youssif In SHAD 2020 Conference Diabetes in real practice
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Drug induced Dysglycemia
Similar to Drug induced Dysglycemia (20)
More from Usama Ragab
More from Usama Ragab (20)
Recently uploaded
Recently uploaded (20)
Drug induced Dysglycemia
- 1. Drug Induced Dysglycemia Usama Ragab Youssif, MD Consultant Internal Medicine Lecturer of Medicine Zagazig University Email: usamaragab@medicine.zu.edu.eg Slideshare: https://www.slideshare.net/dr4spring/ Mobile: 00201000035863 SHAD 2020 - Marriott El-Zamalek Cairo Hotel ā 26 NOV 2020
- 3. Agenda ā¢ Drug induced Dysglycemia ā¢ Mechanisms of Drug induced Dysglycemia ā¢ Risk factors ā¢ Examples for drug induced diabetes e.g. steroid inducedā¦etcā¦ ā¢ Prevention and management will be discussed in each section ā¢ Final bottom line
- 4. Definitions ā¢ A number of medications have side effects which include the raising of blood glucose levels. ā¢ When use of a specific medication has lead to the development of diabetes = Drug induced diabetes ā¢ These may cause glucose control to deteriorate if administered to those with existing diabetes = Drug induced hyperglycemia
- 5. Classification of Diabetes Diabetes can be classified into the following general categories: 1. Type 1 diabetes (due to autoimmune Ć-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive loss of Ć-cell insulin secretion frequently on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or chemical- induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation) Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S14-S31
- 6. 2 Broad Mechanisms ā¢ Some of these cause Ī²- cell destruction but others will cause diabetes by increasing insulin resistance in susceptible individuals or both.
- 7. Drugs that cause or exacerbate hyperglycemia Potentially potent effects Minor or no effects Glucocorticoids COC; with high dose estrogen Thiazide diuretics (doses dependent) Non selective BB B2 adrenoceptor agonists Atypical antipsychotics HAART; Pi, NRTI Pentamidine Gatifloxacin Diazoxide Cyclosporin, Tacrolimus (CNIs) mTORi Streptozocin POP Loop diuretics Calcium channel blockers Growth hormone (physiological doses) Somatostatin analogues Androgen deprivation therapy SSRI Nicotinic acid Lamivudine INH
- 8. Why to remember all of these drugs Many Drugs Have Diabetogenic properties ā¢ Newer generation of drugs ā¢ Polypharmacy in diabetics ā What is happened to my patients??? (worsened-diabetes) ā¢ Various drugs can induce diabetes in previously normoglycemic individuals (new-onset) ā may be reversible or permanent
- 9. Risk Factors General Diabetes risk factors, plus: ā¢ Pre-existing or underlying Diabetes ā¢ Higher doses of the incriminated drugs (steroids, thiazides) ā¢ Use of more than one drug that can induce hyperglycemia: polypharmacy e.g. BB + thiazides (we have many plus in market) Roberts et al., Diabetic Medicine. 2018 Aug;35(8):1011-7.
- 10. Presentations ā¢ New onset diabetes ā¢ Worsening of pre-existing diabetes
- 11. If unknown give cortisone
- 12. Glucocorticoids ā¢ Glucocorticoids were named for their hyperglycemic effects. ā¢ Diabetic symptoms improved following either adrenalectomy or hypophysectomy, so, glucocorticoids have important influences on glucose homeostasis. Selye H . Textbook of Endocrinology. Montreal : Acta Endocrinologica, 1947 . Long. J Exp Med 1936 ;63: 465 ā 490 . Ingle. Endocrinology 1941 ;29: 649 ā 652 .
- 13. Uses and Misuses ā¢ I want to gain weight ā¢ I COLD SHOT ā¢ I have some itching ā¢ I have backache ā¢ Etcā¦
- 14. Glucocorticoids and glucose ā¢ Steroids induced diabetes: Individuals who developed DM in relation to steroid therapy without previous Dx of DM ā¢ Steroids induced hyperglycemia: a more general term covering rise in BG in response to steroids ttt, including those with previous Dx of DM who suffer deterioration in glycemic control Roberts et al., J Br Diabet Soc. 2014;32:126-30.
- 15. Mechanism of GC hyperglycemia
- 16. Adjusted odds ratios for the initiation of hypoglycemic therapy according to average daily glucocorticoid dose in hydrocortisone-equivalent milligrams ā¢ May occur in as low as 7.5 mg prednisolon or equivalent ā¢ Significant hyperglycemia occurs in high doses (i.e. equivalent to 30 mg/day or more of prednisolone) ā¢ Hydrocortisone 20 mg = ļ¼ 5 mg prednisolone = ļ¼ 4 mg methylprednisolone = ļ¼ 0.75 mg dexamethasone Arch Intern Med . 1994 Jan 10;154(1):97-101.
- 17. The route ā¢ Oral ā¢ Parenteral ā¢ Topical (especially in children) ā¢ May in inhaled steroids (wash your mouth) Gomez and Frost. Arch Dermatol 1976 ;112: 1559 ā 1562
- 18. Monitoring for hyperglycemia ā¢ Most commonly used formulations (prednisone) used in once daily dose. ā¢ Rise in the BG starting in mid-morning and continuing throughout the day until bedtime (taking into account the peak effect of these medications (4ā6 hours). ā¢ Measuring FPG only may miss some episodes of hyperglycemia ā¢ An elevation in the FPG can occur with higher doses.
- 19. Prevention ā¢ Adopt steroid free treatment approach ā¢ Use steroid sparing agents ā¢ Sometimes steroids cannot be withdrawn, other measures are often needed to control hyperglycemia.
- 20. Concept of Treatment ā¢ Due to differences in steroid dose and the scheme used, the approach to hyperglycemia should always be individualized. ā¢ When selecting the best treatment the first consideration to make is whether to use oral hypoglycemic drugs or insulin
- 21. Concept of Treatment (cont.) ā¢ Random measure isnāt useful, measure BG frequently (esp pre- lunch or pre-dinner) ā¢ Subjective control is not adequate ā¢ A target blood glucose concentration of <140 mg/dL may be suitable in the short term
- 22. GC & pre-existing DM ā¢ Warn patients that their DM will worsen ā¢ T2D whose controlled by non secretagogues or whose FPG between 126 ā 180 mg/dL will require addition of a sulfonylurea or insulin ā¢ Those poorly controlled with high dosages of oral agent will need insulin therapy
- 23. GC & pre-existing DM (cont.) ā¢ Previous insulin: may need to be increased by 50% initially. ā¢ Titration is the rule ā¢ Adjust up and down: if the steroid dose is reduced or increased by 50%, the insulin dose will be reduced or increased 25%, respectively.
- 24. Which insulin to useā¦ ā¢ Some studies support NPH insulin ā¢ Insulin isophaneās onset of action, peak effect, duration of action closely match the pattern of prednisolone induced hyperglycemia European Journal of Endocrinology (2018) 179, R207āR218
- 25. Basal Longer acting analoguesā¦ ā¢ The use of basal insulin, in addition to prandial insulin, is usually considered when using high doses of steroids are used or previously using it. ā¢ Shift it in the morning rather than evening time Clore JN et al. Endocr Pract. 2009 Prednisolone dose (mg/d) Dexamethasone dose (mg/day) Glargine (u/kg) ā„ 40 ā„ 8 0.4 30 6 0.3 20 4 0.2 10 2 0.1
- 26. Commonly used drugs in glucocorticoids-induced hyperglycemia Drug Adverse effects Metformin Gastrointestinal distress, lactic acidosis, B12 deficiency, contraindicated in renal failure and interactions with other drugs Insulin Hypoglycemia, weight gain Sulfonylureas and Glinides Hypoglycemia, weight gain, cardiovascular risk Incretins (DPP-4 inhibitors and GLP-1 agonists) Gastrointestinal distress, heightened pancreatitis risk Thiazolinediones Weight gain, liquid retention, heightened fracture risk
- 27. An inevitable drug in some people
- 28. Oral contraceptive pills and estrogen replacement therapy ā¢ Estrogens and some progestogens used in COC are potentially diabetogenic. ā¢ Post - receptor insulin resistance appears to be responsible ā¢ High estrogen in old COC generations is risk ā¢ IGT during pregnancy remains a potent risk factor, even with the newer oral contraceptives.
- 29. Good News for COC ā¢ Although COC are associated with metabolic abnormalities, their use is still recommended for women with T1D or T2D without vascular complications and in women with a history of GDM. ā¢ Hyperglycemia induced by hormonal contraceptives is usually reversible on withdrawal of COC ā¢ WHI āin spite of no signal of CV benefit in general populationā, those randomized to HRT had a lower incidence of self - reported diabetes
- 30. Diabetes & Hypertension Walk Hand in Hand
- 31. Thiazide diuretics ā¢ Hyperglycemia was recognized as an adverse effect of chlorothiazide (the first marketed thiazide diuretic) within a year of its introduction in 1957 ā¢ Long - term studies show that IGT usually develops slowly (lag period of 2 years). ā¢ The mechanism involves reduced pancreatic insulin release alone and not reduced insulin sensitivity = remember his cousinā¦
- 32. ā¢ The impairment of insulin secretion is secondary to potassium depletion, which appears to inhibit the cleavage of proinsulin to insulin and is reversible on restoring normokalemia (Each 0.5mEq/L decrease in serum potassium was associated with a 45% higher risk of new diabetes (SHEP) ā¢ Effect appears with high doses ā¢ This effect is so marked in one member of the family, diazoxide: ttt of insulinoma Shafi T. Hypertension. 2009 Feb;53(2):e19. Barry L. Carter. Hypertension. Thiazide-Induced Dysglycemia, Volume: 52, Issue: 1, Pages: 30-36
- 33. Thiazides vs DM: How to Dealā¦ ā¢ These findings were not consistent in literature (see ARIC next slides) ā¢ However, clinicians need to be aware that the thiazide diuretics can affect glucose homeostasis in a dose-dependent manner but the effect appears to be modest. ā¢ The risk is greatly reduced by low-dose therapy (whose benefits therefore outweigh its risks): 12.5-25mg/day HCTZ and replace potassium if found lowā¦
- 34. Take Careā¦ ā¢ Glucocorticoids may cause hypertension and sodium and water retention. ā¢ Thiazide diuretics should not be used to treat these complications, as their own hyperglycemic action synergizes with that of glucocorticoids
- 35. Ī²-Adrenoceptor antagonists ā¢ May be due to weight gain ā Insulin resistance ā¢ Dysglycemic effect amplified if high - dose thiazides combined with BB (we have a lot of plus in markets) ā¢ Risk: high baseline BMI or risk factors of DM ā¢ Not all BB are the same: the risk for new - onset diabetes was 30% greater for atenolol and 34% greater with metoprolol than other agents for example carvedilol stabilized A1c and improved IR in patients with DM and HTN
- 36. Ī²-Adrenoceptor antagonists (cont.) ā¢ The Atherosclerosis Risk in Communities (ARIC) study: +ā 28% in DM over a 6-year period, as compared with other medications. ā¢ The risk conferred by NSBB. ā¢ Prospective study with 12,550 patients ā¢ Hypertension, with no diabetes ā¢ Results: New DM (in BB rather than thiazides) Gress TW et al. N Engl J Med 2000;342:905-912.
- 38. HIV protease inhibitors ā¢ HAART; worsening of pre - existing diabetes or the new onset of T2DM has been reported in 2 ā 6% of patients receiving them. ā¢ May be irreversible ā¢ A striking syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance has also been described in patients receiving HIV protease inhibitors
- 40. Somatostatin analogs ā¢ Somatostatin suppresses insulin and also inhibits the release of the counter - regulatory hormones (GH and glucagon) the net effect in subjects without diabetes is usually to maintain euglycemia. ā¢ Octreotide, a somatostatin analog ļ¼T1D= exogenous insulin + suppressed counter-regulatory hormones = hypo ļ¼T2D= inhibition of endogenous insulin can predominate = hyper ā¢ Lanreotide and the long - acting preparations of both drugs can IGT and occasionally cause diabetes (notably in people with acromegaly whose glucose homeostasis is already impaired).
- 41. Recombinant GH ā¢ Used widely in both pediatric and adult endocrinology practice. ā¢ Many people with adult GHD have abnormal body composition with central adiposity and decreased lean body mass. ā¢ In the short term, rhGH acts as an insulin antagonist but in the longer term leads to increases in IGF - I and decreased fat mass, which tend to improve insulin sensitivity. ā¢ It is recommended, however, that overdosing be avoided and glycemic control be monitored.
- 42. New Onset Diabetes after Transplantation (NODAT)
- 43. Post - transplantation diabetes mellitus (PTDM) ā¢ = New onset diabetes after transplantation (NODAT) ā¢ Definition: diagnosis of diabetes for the first time in the post- transplant period ā¢ Diagnosis is based upon the same criteria for diabetes diagnosis in the general population. ā¢ Overall incidence 4-46% ā¢ Most common in the first few months post transplant.
- 44. Potential mechanism(s) of Drug-induced NODAT Immunosuppressive agent Pathogenic mechanism(s) Comments Corticosteroids See before ā¢ Dose-dependent ā¢ impact of complete withdrawal of chronic low-dose steroids unclear ā¢ Potential āNODAT risk in steroid- free regimens Tacrolimus > CYC-A ā¢ āinsulin secretion (CsA , Tac) ā¢ āinsulin synthesis ā¢ āĪ²-cell density ā¢ Dose-dependent, ā¢ Diabetogenic effect ā with ā steroid dose* Sirolimus ā Peripheral insulin resistance ā¢ impair pancreatic Ī²-cell response ā¢āDiabetogenicity when use with CNis Antimetabolites No increased risk
- 45. Immunosuppressive agent & incidence of DM Immunosuppressive agent Comments TAC +++++ Sirolimus ++++ CYC +++ AZA -- MMF -- Woodward RS. Value Health. 2011 Jun;14(4):443-9
- 46. Diabetes Consultation ā¢ The optimal therapeutic approach remains to be defined but emerging evidence suggests that insulin secretagogues (including the incretin-mimetics) may be the drugs of choice. ā¢ Follow general scheme for diabetes management including OAD or insulin in appropriate setting ā¢ Inattention to PTDM can result in graft failure and other diabetes- related complications
- 47. Transplantation consultation ā¢ Rapid steroid taper (weight against the risk of acute rejection). ā¢ Steroid-sparing or steroid avoidance protocols with priority for graft survival. ā¢ Tacrolimus to cyclosporine conversion therapy??!! No Wayā¦ ā¢ Avoid as possible, CNI and m-TOR inhibitors combination therapy??!!
- 48. | 48 Posttransplantation Diabetes Mellitus (PTDM) CLASSIFICATION AND DIAGNOSIS OF DIABETES 2.18 Patients should be screened after organ transplantation for hyperglycemia, with a formal diagnosis of posttransplantation diabetes mellitus being best made once a patient is stable on an immunosuppressive regimen and in the absence of an acute infection. E 2.19 The oral glucose tolerance test is the preferred test to make a diagnosis of posttransplantation diabetes mellitus. B 2.20 Immunosuppressive regimens shown to provide the best outcomes for patient and graft survival should be used, irrespective of posttransplantation diabetes mellitus risk. E Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S14-S31
- 49. Commonly Encountered in Practiceā¦
- 50. Atypical antipsychotics ā¢ Multifactorial?? Diabetes is more common in schizophrenic ā¢ SGA-induced weight gain the highest potential for weight gain (olanzapine and clozapine) are also associated with the most clinically significant hyperglycemia. ā¢ Many patients receiving these drugs who develop diabetes have traditional risk factors for diabetes. ā¢ Insulin resistance may occur out of proportion of weight gain ā¢ It may occur due to loss of insulin secretion
- 52. How to deal with SGA (monitoring) ā¢ Tableā¦ ā¢ If the person gains 5% or more of their baseline weight during treatment, it is recommended that clinicians consider a switch to another SGA ā¢ Switching from olanzapine to aripiprazole may improve glycemic profile but not necessarily have same control on mental illness ā¢ It is mostly reversible (sometimes not) ā¢ Life style + smoking cessation + psychiatrist consulation Measure ment Baseline 6 Wks 12 Wks Annually Wt & BMI ā Weekly in 1st 6wks ā ā WC ā ā ā ā FPG ā ā ā ā Lipid profile ā ā ā ā BP ā ā ā ā
- 54. Statins ā¢ The HMG CoA reductase inhibitors, commonly known as statins, have been the mainstay of hyperlipidemia and cardioprotection for over two decades but their hyperglycemic potential has only recently been reported. ā¢ The FDA changed the product labeling of statin medications to include the findings of elevated fasting glucose and HbA1c in early 2012. ā¢ Statins appear to increase insulin resistance and decrease insulin secretion, with small increases in HbA1C and fasting glucose.
- 57. Satter et al. Lancet 2010; 375: 735ā42
- 61. Statin is IMPORTANT drug, What a dilemma ā¢ Diabetes and CVD spring from common soil (insulin resistance = metabolic syndrome = cardiometabolic syndrome) ā¢ Prescribe them properly (avoid Statins For All) ā¢ Explain the risk for the patient: tell him the benefit is by far outweigh the risk ā¢ Monitor patients closely especially if more than one proxy of increased metabolic risk is present (I mean component of MS)
- 62. An example of antibiotic
- 63. Fluroquinolones ā¢ Fluoroquinolone-associated dysglycemia appears to be much more common with gatifloxacin (not widely used systemic). ā¢ Of the currently available fluoroquinolones in the USA, moxifloxacin appears to have the highest likelihood for causing hyperglycemia compared to levofloxacin or ciprofloxacin ā¢ Hyperglycemia tends to occur within 1 to 2 weeks of therapy initiation.
- 64. Fluroquinolones (cont.) ā¢ Risk factors: history of DM, high doses, failure to adjust doses in renal insufficiency, acute illness, and age. ā¢ Recent animal studies suggest that hyperglycemia results from 1increased drug accumulation in the pancreas of individuals with diabetes, 2histamine-associated release of the counter-regulatory hormone epinephrine ā¢ Risk of diabetes is not justifying stopping these drugs
- 65. Final Bottom Line ā¢ Many drugs can cause hyperglycemia and diabetes, or worsen blood glucose control in patients with diabetes. ā¢ Drug effects are often reversible and there are often alternative treatments to achieve the same therapeutic goals. ā¢ Where the prescription of diabetogenic drugs is inevitable, careful monitoring of glycemic control and prudent use of suitable antidiabetic treatment can mitigate their effects.
- 66. An ounce of prevention is worth a pound of cure ā¢ Clinician awareness ā¢ Identify high-risk patients ā¢ Monitor blood glucose levels ā¢ Use lowest effective dose for shortest possible duration ā¢ Alter therapy when necessary and possible ā¢ Avoid polypharmacy
Editor's Notes
- A classic example is the nitrosourea, streptozocin (streptozotocin), which has long been used to induce experimental insulin - dependent diabetes in rodents; in humans, it is employed as chemotherapy for inoperable or metastatic insulinoma.
- Risk factors for those at risk of hyperglycaemia with steroid therapy Preāexisting Type 1 or Type 2 diabetes A family history of Type 2 diabetes Previous gestational diabetes Previous impaired fasting glucose or impaired glucose tolerance Polycystic ovarian disease/and or obesity Ethnic minority groups: Pima Indians History of hyperglycemia with steroid use -----
- Mechanism by which GC may induce DM (adapted from Diabetes Textbook 2017e) The main mechanism by which glucocorticoids cause hyperglycemia is through reduction of insulin sensitivity in the liver, skeletal muscle and adipocyte, by approximately 50ā70%, which appears to be dose-dependent. Glucocorticoid administration leads to decreased glucose transport 4 (GLUT-4) expression and migration, decreased glycogen synthesis, and increased hepatic gluconeogenesis. They have also been shown to decrease insulin production and secretion. ------------------ Other mechanisms Corticosteroids increase endogenous glucose production, increment in gluconeogenesis and antagonizing the metabolic actions of insulin Enhance the effects of other counterregulatory hormones, such as glucagon and epinephrine, which increase the endogenous synthesis of glucose Also been shown that the expression of the nuclear receptor peroxisome proliferator-activated receptor Ī± is necessary for the increment in endogenous glucose production induced by corticosteroids Corticosteroids reduce peripheral glucose uptake at the level of the muscle and adipose tissue Costicosteroids also inhibit the production and secretion of insulin from pancreatic Ī²-cells and induce Ī²-cell failure indirectly by lipotoxicity. -------------- Other story: Increase in insulin resistance with increased glucose production and inhibition of the production and secretion of insulin by pancreatic Ī²-cells GCs increase endogenous glucose production, increment in gluconeogenesis and antagonizing the metabolic actions of insulin Enhance the effects of other counterregulatory hormones, such as glucagon and epinephrine, which increase the endogenous synthesis of glucose GCs reduce peripheral glucose uptake at the level of the muscle and adipose tissue GCs also inhibit the production and secretion of insulin from pancreatic Ī²-cells and induce Ī²-cell failure indirectly by lipotoxicity Impairment of gut islet axis (impaired insulinotropic effects of GLP-1)
- All glucocorticoids cause dose - dependent insulin resistance at dosages greater than the equivalent of 7.5 mg/day prednisolone ----- The hyperglycemic potency of glucocorticoids does not follow the hierarchy of their anti - inflammatory or immunosuppressive activities. For example, deflazacort, which has similar immunomodulating effects to other glucocorticoids, produces less hyperglycemia than prednisone or dexamethasone.
- Most problems have been reported with oral glucocorticoids, but those administered topically can also induce severe hyperglycemia, especially if given at high dosage over large areas of damaged skin and under occlusive dressings. This is more likely to occur in children because of their higher ratio of total body surface area to body weight.
- The most common clinical presentation of glucocorticoidinduced hyperglycemia is a rise in the blood glucose starting in mid-morning and continuing throughout the day until bedtime. Therefore, this adverse drug reaction may not be detected if only the fasting blood glucose is monitored. ----- Oral glucocorticoids are typically administered so that they mimic the physiologic pattern of endogenous cortisol secretion, and once daily glucocorticoids such as prednisone and prednisolone are administered in the morning. Taking into account the peak effect of these medications after a dose (e.g. peak effect of prednisone at 4ā6 hours), checking a 1ā to 2-hour post-lunch or a pre-dinner blood glucose starting a few days after initiation of treatment will enable detection of any hyperglycemia. ----- People with pre-existing diabetes should monitor their blood glucose more frequently during the course of glucocorticoid treatment and all patients should also be advised to monitor for symptoms of hyperglycemia.
- Management depends primarily upon the severity of hyperglycemia. Random blood glucose measurements provide only an approximate guide, and therapy should be adjusted by frequent blood glucose monitoring; simple relief of symptoms alone is inadequate. A target fasting blood glucose concentration of <140 mg/dL may be suitable in the short term, and the usual criteria for good control should be applied if long - term glucocorticoid therapy is undertaken. If significant hyperglycemia develops with high - dose glucocorticoid therapy (e.g. prednisolone 40 mg/day or more), insulin therapy may be started at 0.4 ā 0.5 U/kg bodyweight per day, divided between morning and evening doses of short - and intermediate-acting insulin. This dosage is unlikely to produce hypoglycemia and indeed may need to be increased progressively, as dictated by blood glucose monitoring. If the patient presents as a hyperglycemic emergency, standard therapy with intravenous insulin should be started; because steroids induce insulin resistance, insulin delivery rates of 6 ā 8 U/hour may be required initially. Patients with diabetes who are to begin high - dosage glucocorticoid therapy must be warned that their glycemic control will worsen, and treatment for their diabetes should be adjusted prospectively. Those with T2DM treated by diet alone and whose fasting blood glucose concentration is 7 ā 10 mmol/L will require addition of a sulfonylurea or insulin, while those poorly controlled with high dosages of oral agent will need insulin therapy. For patients already taking insulin, the dosage may need to be increased by 50% initially, starting on the same day as steroid therapy. Further adjustments will be based upon results of blood glucose monitoring.
- ŁŁŁ Ų© Ų§ŁŲ³Ų± ŁŁ Ų¹ŁŲ§Ų¬ Ų£Ł Ų³ŁŲ± ŁŁ Ų§Ł individualization
- Simple relief of symptoms alone is inadequate. A target fasting blood glucose concentration of <140 mg/dL may be suitable in the short term, and the usual criteria for good control should be applied if long - term glucocorticoid therapy is undertaken.
- Patients with diabetes who are to begin high - dosage glucocorticoid therapy must be warned that their glycemic control will worsen, and treatment for their diabetes should be adjusted prospectively.
- For patients already taking insulin, the dosage may need to be increased by 50% initially, starting on the same day as steroid therapy. Further adjustments will be based upon results of blood glucose monitoring. ----- Insulin therapy offers the flexibility of matching the onset, peak, and duration of action to the pattern and degree of hyperglycemia the individual is experiencing; furthermore the dose can be more easily adjusted when the glucocorticoid dose is changed. ------- Because many courses of treatment with glucocorticoids consist of an initial high dose with a gradual taper to physiologic level and then discontinuation, careful monitoring of blood glucose and subsequent insulin dose adjustments may be necessary to avoid hypoglycemia as the medication is being withdrawn.
- Impaired glucose tolerance during pregnancy remains a potent risk factor, even with the newer oral contraceptives; these women are three times more likely to develop diabetes with a progestogen -only pill than with a low - dose combined pill.
- Remember his cousin
- SHEP = Systolic Hypertension in the Elderly Program ----- Thus, the change in plasma K+ appears to be related inversely to blood glucose, but how? The well-described effects of hyperkalemia to stimulate insulin secretionĀ (arrow āBā inĀ Figure) and insulin to induce cellular uptake of potassiumĀ suggest that low plasma potassium could impairĀ insulin secretion and thereby increase plasma glucose. Hypothesis A+B=C is denoted inĀ Figure. ---------- The severity of glucose intolerance is strongly correlated with the degree of hypokalemia; the impairment of insulin secretion is secondary to potassium depletion, which appears to inhibit the cleavage of proinsulin to insulin and is reversible on restoring normokalemia. The result is post - prandial hyperglycemia, with elevated proinsulin concentrations between meals that may downregulate insulin receptors in peripheral tissues. This phenomenon affects people without diabetes and those with T2DM, but not patients with type 1 diabetes (T1DM) receiving exogenous insulin replacement. ---------- Historically, thiazide-induced dysglycemia has been connected to alterations in potassium balance, namely hypokalemia. Since insulin secretion is linked, in part, to an accumulation of intracellular potassium within the pancreatic Ī² cell, potassium loss would impair insulin release resulting in hyperglycemia. In an effort to substantiate this long-held belief, a group of investigators reviewed pertinent intervention trials using thiazides from 1966ā2004 that measured serum potassium and glucose levels. Fifty-nine trials met inclusion criteria. Analysis of the trial data supported an inverse relationship between potassium balance and blood glucose levels. However, the effects on blood glucose were modest with an average increase of 7.1 mg/dL Ā± 7.38; 0.4 mmol/L Ā± 0.4). In a subgroup analysis of the above-mentioned SHEP trial, for every 0.5 mEq/L decrease in serum potassium there was a corresponding 45% increase in incident diabetes risk (95% CI: 24ā70%; p <0.001). This association was only evident during the first year of treatment with chlorthalidone. In a more recent subgroup analysis, no correlation was found between fasting serum glucose and serum potassium levels in people with hypertension receiving hydrochlorothiazide alone and when added to atenolol .
- ŁŲŲ³Ł Ų§ŁŲŲø Ų§ŁŲ¬Ų±Ų¹Ų§ŲŖ Ų„ŁŁŁ Ų„ŲŁŲ§ Ų¹Ų§ŁŲ²ŁŁŲ§ ŁŁ Ų¹ŁŲ§Ų¬ Ų§ŁŲ¶ŲŗŲ· Ł ŁŲ“Ł Ų¹Ų¶ŁŲ© Ų§ŁŁŁŲØ ŁŁ ŲØŲ§ŁŲ£Ų³Ų§Ų³ Ų¬Ų±Ų¹Ų§ŲŖ ŁŁŁŁŲ© ŲØŲ³ Ų¢Ų®ŲÆ ŲØŲ§ŁŁ Ł Ų“ ŁŁ ŲÆŁŲ§ Ų¶ŲŗŲ· Ų£Ų³ŲŖŲ®ŲÆŁ Ł ŁŁŁŁ ŲØŁŲ§Ų³
- Hypothesis: To determine if thiazide diuretics and beta-blockers promote the development of type 2 diabetes mellitus. Principal Findings: There were 29.1 new cases of diabetes per 1000 patient years among hypertensive subjects versus only 12.0 per 1000 patient years in nonhypertensive subjects (RR 2.43, 95% 2.16-2.73). After adjustments for multiple risk factors (age, sex, race, education, adiposity, fmaliy history, activity level, coexisting illnesses), hypertensive subjects who were taking thiazide diuretics were not at increased risk for developing diabetes compared to hypertensive subjects not on any antihypertensive therapy (relative hazard 0.91, 95% CI 0.73-1.13). Subjects taking ACE inhibitors or calcium channel antagonists were also not at increased risk than those not taking any medication. In contrast, hypertensive subjects taking beta-blockers had a significantly higher risk of devloping type 2 diabetes (relative hazard 1.28, 95% CI 1.04-1.57). Interpretation: Type II diabetes mellitus was more than twice as likely to develop in those with hypertension than in normotensive persons. The use of thiazide diuretics in hypertensive individuals did not increase the risk of developing diabetes. In contrast, the use of beta-blockers was associated with an increased risk of developing diabetes.
- The effect of long ā acting somatostatin analogs on glucose metabolism in patients with acromegaly is complex; they reduce the insulin resistance caused by elevated growth hormone concentrations, but also suppress insulin secretion from islet Ī²- cells. The net balance between the two effects determines whether long - acting somatostatin analogs improve or worsen glucose metabolism. These effects are inconsistent and unpredictable, with worsening glucose metabolism occasionally seen in the presence of improving growth hormone concentrations. Utilizing its suppressive effect on insulin release, octreotide has been used effectively to manage refractory hypoglycemia caused by acute sulfonylurea poisoning or quinine treatment.
- Pre-disposing factors ļ®Genetics ļ®Metabolic syndrome ļ®Increasing age
- PTDM has been reported in non - diabetic adult transplant recipients taking ciclosporin (cyclosporine). PTDM is also commonly observed in up to 28% of adults receiving tacrolimus (FK506). Animal studies have implicated reversible Ī²- cell damage, causing reduced insulin secretion (mainly). Trials comparing the incidence of NODAT in CSA Vs Tac treated patients have yielded mixed results. Tac has been shown to have a greater diabetogenic effect (questionable??). ---------- Trials comparing the incidence of NODAT in cyclosporine A(CSA) Vs. tacrolimus (Tac)-treated patients have yielded mixed results Inconsistencies may be due to differences in the definition of NODAT and drugs. Tac has been shown to have a greater diabetogenic effect. In one study, the incidence of NODAT at 6-month in CSA Vs. tacrolimus was 26% Vs.33.6% In Tac-treated patients with HCV, the incidence of NODAT was much higher than in CSA-treated patients (57.8% versus 7.7%, P , 0.0001). Whether concomitant exposure to tacrolimus and HCV plays a synergistic role in the development of NODAT remains speculative. ----------- This limits the application of these agents in the prevention of type 1 diabetes, and helps explain the high prevalence of post-transplantation diabetes, observed in 13.4% of patients following solid-organ transplantation (16.6% for tacrolimus vs 9.8% for ciclosporin) ---------- Alterations in insulin sensitivity and impaired Ī²-cell function are cited as causative factors in the development of glucose intolerance. However, recent evidence corroborates findings that defective insulin secretion is the primary pathologic defect. ----------- Steroid = discussed before. mTORi e.g. sirolimus: early trials suggested that sirolimus was devoid of any diabetogenic effects either alone or in combination with CNI. Later studies confirmed the diabetogenicity of sirolimus. Antiproliferative: AZA and MMF have not been shown to be diabetogenic, even??, the concomitant use of MMF has been suggested to decrease the diabetogenic effect of Tac. ------------ Sirolimus in combination with a CNI (CsA or Tac) had the highest incidence of NODAT. patients treated with (Sir + Tac) combination therapy had a hazard ratio of developing NODAT of 1.9 compared with those receiving (Tac + MMF/AZA), suggesting the independent risk of NODAT associated with sirolimus. -------------
- More recent trials, suggest the risk of developing PTDM can be reduced by the use of low - dose tacrolimus (0.15 ā 0.2 mg/kg/day). The diabetogenic effects of both ciclosporin and tacrolimus are largely reversible with appropriate reductions in the drug dosage.
- For many reasons, A1c as a basis for diagnosis is not recommended in NODAT.
- Diabetes is, for example, considered to be 2-3 times as common in people with schizophrenia as in the background population, probably because of lifestyle factors such as obesity and lack of exercise, although a family history of diabetes is common in those with schizophrenia. ----- Maximum weight gain occurs in the first year of therapy and is related to the duration of exposure. Increased appetite and consequent food intake, reduced satiety, and effects on adipose tissue like increased lipogenesis contribute to weight gain. Animal studies also suggest that SGAs may induce hyperglycemia through inhibition of insulin secretion by antagonism of alpha-1 adrenergic, muscarinic (M3), and serotonergic (5HT2) receptors.
- Second-generation antipsychotic use requires scheduled monitoring of glucose, lipids, blood pressure, and body mass index. ----- However, if significant weight has been gained over the course of the treatment. Insulin resistance and type 2 diabetes may be permanent.
- Statins appear to increase insulin resistance and decrease insulin secretion, with small increases in HbA1c and fasting glucose (mechanisms by which statins induce and aggravate diabetes include impaired pancreatic secretion of insulin (by blocking calcium channels), reduced expression of GLUT4 interfering with glucose uptake and disposal by skeletal muscle, and exacerbation of insulin resistance in liver and peripheral tissues). Statins are also known to worsen glycemic control in patients with DM. The risk for DM with statins is more pronounced in those who already have the traditional risk factors.
- The JUPITER trial reported that, for those with one or more diabetes risk factors, rosuvastatin was associated with a 28% increase in diabetes but 134 cardiovascular events or deaths were avoided for every 54 new cases of diabetes. ASCOT-LLA= ator HPS= simvastatin JUPITER= rosuvastatin WOSCOPS= pravastatin LIPID= CORONA= rosuvastatin PROSPER= pravastatin MEGA= pravastatin AFCAPS= lovastatin 4S= simvastatin ALLHAT= pravastatin GISSI PREV=rosuvastatin
- JUPITER 17,802 healthy men and women with LDL < 130mg/dL and high-sensitivity C-reactive protein levels ā„ 2md/L were assigned to rosuvastatin 20mg QD or placebo (1:1) and were followed for occurrence of cardiovascular events An unexpected finding through physician reports regarding newly diagnosed cases of diabetes during the follow-up period Statins, as a class, increase the risk of incident diabetes However, individual statin data showed that statins have a variable effect. ------
- ŁŲ¹ŁŁ ŁŁ Ų·ŁŲ¹ŲŖ Ł Ų²Ų±Ų¹Ų© ŲØŲŖŁŁŁ ŁŁ Ł Ų¶Ų§ŲÆ ŲŁŁŁ Ł Ų¹ŁŁ ŁŲØŁŁ ŁŲ§Ų²Ł Ų£Ų³ŲŖŲ®ŲÆŁ Ł
- When evaluating a possible case of drug-induced dysglycemia, a careful review of prescription and non-prescription (over-the-counter) medications as well as herbal products and dietary supplements can reveal possible offenders. In addition to a thorough drug history, the clinician should also evaluate the patientās drug regimen and comorbid conditions that may affect the pharmacokinetics or pharmacodynamics of the suspected drug. ----- Baseline data such as weight and fasting blood glucose levels should be obtained when appropriate. This is especially important in people taking more than one medication with the potential for hyperglycemia, prescribed a high dose of the medication, taking concomitant drugs that can increase the concentration or duration of the medication, or those with other risk factors for diabetes.