diabetes mellitus type 1 (insulin-dependent, juvenile)
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Etiology
- genetic susceptibility
- environmental trigger
- cow's milk may contain environmental trigger[10]
- enterovirus infection[11]
- increased maternal gluten intake[56]
- autoimmune destruction of pancreatic islet beta-cells
- pregnancy[2]
- myocardial infarction[2]
- idiopathic
Epidemiology
- 10% of elderly with newly diagnosed diabetes[3]
- among U.S. adults with type-1 diabetes, median age of onset 24 years[67]
- later for men than women 27 vs 22 years[67]
- peak onset at 12 years[67]
- late-skewed distribution with case occurring in elderly > 70 years[67]
Pathology
- insulin deficiency
- hyperglycemia
- autoimmune disease results in pancreatic islet beta-cell dysfunction*
- serum autoantibodies to beta-cell antigens
- anti-insulin[6]
- anti-glutamic acid decarboxylase-2 (GAD2)
- anti-PTPRN, anti-PTPRN2
- after presenting episode of diabetic ketoacidosis, a 'honeymoon phase' may follow in which remaining functional pancreatic beta-cells regain ability to produce some insulin[2]
- high levels of advanced glycation end products (AGEs) increases risk of any complication[13]
* also see Comparative biology (below)
Genetics
- linked to certain HLA-DR & DQ loci
- 50% concordance in monozygotic twins
- susceptibility linked to CTLA4, HNF1A
- defects in VEGFA & SOD2 are a cause of susceptibility to microvascular complications of diabetes mellitus type 1
Clinical manifestations
- polyuria
- polydipsia
- polyphagia
- weight loss
- blurred vision
- peripheral neuropathy
- classic stocking-glove pattern
- foot paresthesias
- cranial nerve III palsy
- classic stocking-glove pattern
- stiff hand syndrome
- pruritus
- abdominal pain
- orthostasis
- delirium
- xanthomas
- signs of dehydration
- signs of autoimmune disease
Laboratory
- urinalysis
- urine glucose
- urine ketones
- urine protein
- urine albumin/creatinine ratio
- 5 years after initial diagnosis, annually thereafter[2]
- serum chemistries
- serum glucose
- seum urea nitrogen
- serum creatinine (eGFR)
- serum ketones
- serum C peptide (low)
- fasting lipid panel at diagnosis & annually thereafter[2]
- hemoglobin A1c
- every 6 months
- every 3 months if treatment is being adjusted to optimize glycemic control[2]
- avoiding hypoglycemia takes precedence over achieving HbA1c targets[41]
- target HgbA1c is < 7%, < 8% if history of clinically significant hypoglycemia[41]
- target of HgbA1c < 6.5% in newly-diagnosed diabetes, long life expectancy & no cardiovascular disease[41]
- target for pediatric patients is 7.5%[22]
- 1,5-anhydroglucitol in serum (GlycoMark) is used primarily to identify glycemic variability in patients with normal to near normal hemoglobin A1c
- serology (diabetes-associated autoantibodies)
- point of care testing: capillary blood glucose
- 3 AM capillary blood glucose for fluctuating AM capillary blood glucose
- see ARUP consult[19]
* recommended for initial confirmation of type 1 diabetes[2]
Diagnostic procedures
- ophthalmoscopy to screen for diabetic retinopathy
- 5 years after initial diagnosis, annually thereafter[2]
- 10 g monofilament exam, 128 Hz tuning fork & ankle reflexes
- 5 years after initial diagnosis, annually thereafter[2]
Complications
- also see diabetes mellitus complications
- diabetic ketoacidosis
- untreated, or inadequately treated type-1 diabetes[2]
- often a precipitating event: infection, pregnancy ...
- increased risk of epilepsy (5-fold)
- epilepsy increases risk of diabetic ketoacidosis[15]
- hypoglycemia
- treat with glucose &/or glucagon
- look for changes in insulin requirements (renal failure ...)
- lowering insulin dose may restore sensitivity to hypoglycemia (awareness) as well as prevent further episodes of hypoglycemia
- several weeks may be required[2]
- heart failure: hazzard ratio = 4 for HgbA1c > 10.5% vs < 6.5%[14]
- cheiroarthropathy
- increased risk of cardiovascular mortality & all-cause mortality, even those with well-controlled glycated hemoglobin (HgbA1c < 7%)[25][27]
- life-expectancy shortened by 13 years[27]
- women with greater loss of life expectancy than men
- reduced life expectancy even among diabetics with preserved renal function[27]
- HgbA1c > 9.7% confers even higher mortality
- cardiovascular mortality & all-cause mortality higher in women than in men[28] (RR.1.37)
- earlier age at onset associated with increased risks for cardiovascular disease & mortality, especially among women[51]
- life-expectancy shortened by 13 years[27]
- poor glycemic control around conception is associated with increased risk for congenital heart disease[50]
- autoimmune diabetes associated with other autoimmune diseases
- gastroparesis
- frozen shoulder, carpal tunnel syndrome, trigger finger, & Dupuytren contracture are common[66]
- also see diabetes mellitus complication
Differential diagnosis
- ketosis-prone type 2 diabetes may present with DKA (diabetic ketoacidosis)
Management
delay of progression
- teplizumab (Tzield) an anti-CD3 monoclonal antibody is FDA-approved to prevent progression of type-1 diabetes from stage 2 to stage 3, the irreversible stage when insulin-producing beta-cells lose ability to maintain normal glycemic control[60]
- verapamil 60-120 mg/day escalating every 2-4 weeks to 360 mg/day maximum (> 50 kg) partially preserves stimulated C-peptide secretion at 52 weeks[62]
- intensive glycemic control through automated insulin delivery does not affect the decline in pancreatic C-peptide secretion at 52 weeks[62]
insulin
- basal insulin QHS to account for 50% of daily insulin[2]
- premeal blood glucose target 80-130 mg/dL[26]
- short-acting insulin 5-15 minutes premeal
- regular insulin 30 minutes premeal[2]
- premeal blood glucose target 80-130 mg/dL[26]
- conventional (simple) SQ dosing:
- insulin 70/30 (70% NPH/30% regular) 2/3 in AM, 1/3 in PM
- lacks elegance, but may result in better compliance
- intensified SQ therapy
- regular insulin 1/4 of daily dose TID before meals
- NPH, Lente, or glargine 1/4 of daily dose QHS
- NPH may also be dosed BID
- mealtime dosage adjusted by patient using finger stick glucose according to algorithm
- rapid-acting inhaled insulin is noninferior to aspart insulin for HbA1c & less likely to cause hypoglycemia[41]
- adjustments of +/- 10% of mealtime & QHS insulin based on 3 day trends
- increase QHS insulin for elevated AM preprandial glucose
- fluctuating AM preprandial glucose may be associated with overnight hypoglycemia (measure 3 AM blood glucose)
- fluctuating mealtime glucose may be due to mismatch of short-acting insulin administration with meals[2]
- may reduce atherosclerosis (carotid stenosis)[5]
- may slow progression of renal impairment[17]
- may diminish long-term mortality (6% vs 9%) over span of 27 years[27]
- may slow loss of endogenous insulin secretion when implemented in early phases of type 1 diabetes[2]
- monitoring of glycemic control
- physiologic glycemic control can reduce microvascular complications by 34-76%[2]
- frequent glucose self- monitoring >= 6x/day with intensive insulin therapy[2][41]
- continuous glucose monitoring superior to conventional monitoring
- adults who need multiple insulin injections daily[36][41][58]
- insulin pump therapy[2]
- hospitalized patients[2]
- critically ill patients require intravenous insulin with dosing based on a validated algorithm with point-of-care monitoring every 1-2 hours
- non critically ill patients require basal insulin in addition to prandial insulin
- sole use of insulin sliding scale is not recommended[2]
- external insulin pump
- provides tighter glucose control in selected patients
- reduces fatal cardiovascular events (RR=0.58) & all-cause mortality (RR=0.73) relative to daily insulin injections[29]
- contraindications:
- automated closed-loop insulin delivery (artificial pancreas) is investigational (2011)[12]
- sensor-augmented insulin pump therapy[58]
- continuous subcutaneous insulin infusion
- cost-effective for patients unable to achieve adequate glycemic control with multiple daily insulin injections[2]
- large glycemic variability, hypoglycemia (esp unawareness)[2]
- switch to continuous glucose monitoring
- patient education & training in insulin delivery rather than choice between an insulin pump or injections may be key[38]
- insulin pumps should not be provided to adults with poor glycemic control until the effects of training on participants' level of engagement in intensive self management have been determined[38]
- young patients with type 1 diabetes may experience fewer complications (including hypoglycemia & diabetic ketoacidosis) with insulin pump than with insulin injections[42]
- continuous glucose monitoring with multiple insulin injections described as less expensive alternative to insulin pump[46]
- dosage requirements may diminish in the ;honeymoon phase' (see pathology)
- avoid regimens that include insulin sliding scale
- correctional insulin is additional premeal insulin for preprandial glucose not at target[2]
other hypogylcemic agents
- metformin does not improve glycemic control in overweight/ obese adolescents with diabetes mellitus type 1[30]
- insulin plus liraglutide may improve glycemic control relative to insulin alone
- insulin plus liraglutide plus dapagliflozin lowers hemoglobin A1c but may increase risk for ketoacidosis[33]
- insulin plus dapagliflozin (5-10 mg QD) lowers hemoglobin A1c
- insulin plus sotagliflozin improves glycemic control. but is associated with excess risk of diabetic ketoacidosis[57]
- metabolic outcomes were more favorable with GLP-1 agonists (glutides) than with SGLT-2 inhibitors (flozins)[63]
hypoglycemia
- generally managed with oral glucose or other carbohydrate
- glucagon may be prescribed to high-risk patients for administration by family members, caregivers, or school personnel[41]
- patients with clinically significant hypoglycemia should raise their glycemic targets transiently for several weeks[41]
- switching from NPH to degludec, detemir or glargine may reduce frequent episodes of hypoglycemia & improve glycemia control[65]
- continuous glucose monitoring may reduce episodes of hypoglycemia[2]
diet
- total calories 25 times desirable body weight in kg
- total fat < 30% of calories
- saturated fat < 10% of calories
- cholesterol < 300 mg/day
- distribution of calories
- a very low-carbohydrate diet may reduce HgbA1c by 1.4%[48]
activity
- take a break from prolonged sitting every 30 minutes[35]
- regular aerobic exercise[37]
- at least 150 minutes of physical activity every week[35]
- all-types of exercise improve glycemic control[64]
- no more than 2 consecutive days without activity[35]
- 2-3 days/week of flexibility or balance training, such as tai chi or yoga for older adults with diabetes[35]
- precautions
- check fasting glucose prior to vigorous exercise
- rapidly absorbed carbohydrate prior to extended exercise if glucose is low
- reducing doses of mealtime insulin helpful for exercise-induced hypoglycemia[2]
- avoid exercise within 4 h of regular insulin
- avoid jogging/ running if neuropathy or peripheral vascular disease is present
- avoid resistance training if retinopathy is present due to risk of ocular hemorrhage
- exercise results in increases hepatic gluconeogenesis &/or glycogenolysis resulting in hyperglycemia[2][21]
- post exercise metabolism, however, can result in hypoglycemia
- >= 45 grams of complex carbohydrates at bedtime to prevent nocturnal hypoglycemia after evening exercise[2]
- limit or abstain from alcohol after exercise
- alcohol inhibits hepatic gluconeogenesis[2]
- avoid evening exercise if fluctuating AM preprandial blood glucose (overnight hypoglycemia)
- also check 3 AM capillary blood glucose for Somogyi effect[2]
preventive medicine
- renal protection:
- ACE inhibitor/ARB not effective;[7]
- ARB may actually worsen albuminuria[7]
- neither ACE inhibitor or statin reduces albuminuria in adolescents[43]
- use of ACE inhibitors or ARBs not recommended for patients with normal blood pressure & urine albumin/creatinine < 30 mg/g & eGFR > 60 mL/min/1.73 m2[1]
- avoid flozins (not FDA-approved for type 1 diabetes)
- diabetic retinopathy:
- screening within 5 years of diagnosis or at puberty[45]
- ACE inhibitor/ARB may benefit 2/3 of patients[7]
- aspirin 81 mg QD (75-162 mg)
- men > 50 & women > 60 years with additional cardiac risk factors & not at risk for bleeding[2][8][9]
- optional for older patients without additional cardiac risk factors[9]
- younger patients at high risk
- aspirin reduces risk of serious vascular events (RR=0.88) but increases risk of major bleeding (RR=1.3)[53]
- fasting lipid panel annually
- treat dyslipidemia
- LDL cholesterol target < 70 mg/dL (2023 ADA)[61][2] or < 55 mg/dL if high cardiovascular risk
- lower total cholesterol < 135 mg/dL regardless of LDL cholesterol[2]
- statin of benefit in patients > 40 years of age & at least 1 additional cardiovascular risk factor[2]
- statin treatment based on individual risk rather than LDL cholesterol[26]
- high-intensity statin therapy (atorvastatin, rosuvastatin)
- known cardiovascular disease (secondary prevention)
- LDL cholesterol > 190 mg/dL
- 10 year risk of cardiovascular event > 7.5%[2]
- atorvastatin, rosuvastatin & simvastatin best statins for lowering non-HDL cholesterol in patients with diabetes mellitus[59]
- other (moderate intensity) statins for patients >= 40 years of age with 10 year risk of cardiovascular event < 7.5%[2]
- serum triglycerides target < 150 mg/dL
- use of fibrates[2] weakly (at best) supported by results of the Field study
- do not use niacin (hyperglycemic effect)
- metformin of no benefit in mitigating atherosclerosis[39]
- no benefit in omega-3 fatty acids for cardiovascular disease[54]
- exercise stress testing if
- age > 50 years
- abnormal ECG
- additional cardiovascular risk factor[2]
- blood pressure (BP)
- eye exam
- ophthalmologic evaluation after 3-5 year of disease or at puberty
- funduscopic examination annually[2]
- foot care
- inspect feet for deformity, ulceration, vascular insufficiency every 6 months
- deep tendon reflex at ankles
- vibratory & light pressure thresholds in feet
- foot inspection each visit[2]
- peripheral neuropathy:
- gabapentin, carbamazpeine, TCA, capsaicin
- gastroparesis
- small feedings, metoclopramide, bethanechol
- erectile dysfunction: phosphodiesterase inhibitor
- vaccinations:
patient education
- insulin injection technique
- finger stick capillary glucose technique
- factors influencing blood sugar
- signs & symptoms of hypoglycemia*
- glucagon IM if found unresponsive (friends & family)
- foot care
- group sessions ineffective[18]
- patient training program used in REPOSE trial[39]
other
- assessment of disease progression
- hemoglobin A1c every 3-4 months[2]
- target A1c < 7%
- urinary albumin/creatinine ratio annually
- hemoglobin A1c every 3-4 months[2]
- preservation of beta-cell function
- pancreatic islet cell transplantation
- generally in association with renal transplantation
- human pluripotent stem cells may be induced to form glucose-responsive, insulin-secreting beta cells
- the process is reported to be scalable to produce large quantities of such cells[24]
- anti-CD3 monoclonal antibody IV for 2 weeks preserved insulin secretion in patients with newly diagnosed type 1 diabetes[4]
- two doses of BCG vaccine may improve glycemic control[49]
- HgbA1c 6.2% vs 7.1% after 3 years
- prevention
- oral insulin not useful in high-risk persons[44]
* beta blockers may mask signs & symptoms of hypoglycemia
Comparative biology
- in vitro beta cell production in combination with a delivery system consisting of beta cells encased in cages of nonreactive alginate restored glycemic control in mice with induced type 1 diabetes & maintained it for 6 months[32]
- the alginate cages protected the beta cells from the mice's immunologic responses (apparently cell-mediated) & themselves did not evoke a foreign body response
More general terms
More specific terms
- brittle diabetes mellitus
- genetic form of insulin-dependent diabetes mellitus
- neonatal diabetes mellitus
Additional terms
- blood pressure & hypertension in diabetes
- diabetes mellitus complication
- diabetics who become pregnant
- glycemic control
- hyperglycemia
- immune dysfunction in diabetes mellitus
- insulin pump
References
- ↑ 1.0 1.1 Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 626-628
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 2.35 2.36 2.37 2.38 2.39 2.40 2.41 2.42 2.43 2.44 2.45 2.46 2.47 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17. 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 3.0 3.1 Peters A. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 4.0 4.1 4.2 Journal Watch 22(12):93, 2002 Diabetes Prevention Trial - Type 1 Diabetes Study Group N Engl J Med 346:1685, 2002 Herold KC et al, N Engl J Med 346:1692, 2002
- ↑ 5.0 5.1 Journal Watch 23(13):107, 2003 Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, O'Leary DH, Genuth S; Diabetes Control and Complications Trial; Epidemiology of Diabetes Interventions and Complications Research Group. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med. 2003 Jun 5;348(23):2294-303. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12788993
- ↑ 6.0 6.1 6.2 Journal Watch 25(13):105, 2005 Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005 May 12;435(7039):220-3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15889095
Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature. 2005 May 12;435(7039):224-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15889096 - ↑ 7.0 7.1 7.2 7.3 Mauer M et al Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes N Engl J Med 2009 361:40-51 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19571282 <Internet> http://content.nejm.org/cgi/content/short/361/1/40
Perkins BA et al Diabetes complications and the renin-angiotensin system. N Engl J Med 2009 Jul 2; 361:83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19571288 - ↑ 8.0 8.1 Pignone M et al Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes: A Position Statement of the American Diabetes Association, a Scientific Statement of the American Heart Association, and an Expert Consensus Document of the American College of Cardiology Foundation Circulation. 2010 May 27 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20508178 <Internet> http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3181e3b133v1
Pignone M et al Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes: A Position Statement of the American Diabetes Association, a Scientific Statement of the American Heart Association, and an Expert Consensus Document of the American College of Cardiology Foundation Diabetes Care. 2010 Jun;33(6):1395-402. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20508233 - ↑ 9.0 9.1 9.2 Prescriber's Letter 17(7): 2010 COMMENTARY: Aspirin for Primary Prevention in Patients with Diabetes PATIENT HANDOUT: Aspirin and Your Heart PATIENT HANDOUT SPANISH VERSION: La Aspirina y el Corazon GUIDELINES: Aspirin for Primary Prevention of Cardiovascular Events in People with Diabetes Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260708&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 Knip M et al Dietary Intervention in Infancy and Later Signs of Beta-Cell Autoimmunity N Engl J Med 2010; 363:1900-1908, November 11, 2010 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21067382 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1004809
- ↑ 11.0 11.1 Yeung W-CG et al. Enterovirus infection and type 1 diabetes mellitus: Systematic review and meta-analysis of observational molecular studies. BMJ 2011 Feb 3; 342:d35 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21292721
Hober D and Sane F. Enteroviruses and type 1 diabetes. BMJ 2011 Feb 3; 342:c7072. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21292717 - ↑ 12.0 12.1 Hovorka R et al. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: Crossover randomised controlled studies. BMJ 2011 Apr 14; 342:d1855. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21493665
- ↑ 13.0 13.1 Sun JK et al. Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: The Joslin 50-year medalist study. Diabetes Care 2011 Apr; 34:968. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21447665
- ↑ 14.0 14.1 Lind M et al Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: an observational study The Lancet, Early Online Publication, 25 June 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21705065 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960471-6/abstract
- ↑ 15.0 15.1 Schober E et al. Association of epilepsy and type 1 diabetes mellitus in children and adolescents: Is there an increased risk for diabetic ketoacidosis? J Pediatr 2011 Nov 7 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22056281 <Internet> http://www.sciencedirect.com/science/article/pii/S0022347611010080
- ↑ 16.0 16.1 16.2 Centers for Disease Control and Prevention Use of Hepatitis B Vaccination for Adults with Diabetes Mellitus: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR December 23, 2011 / 60(50);1709-1711 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6050a4.htm
- ↑ 17.0 17.1 The DCCT/EDIC Research Group. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 2011 Dec 22; 365:2366. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22077236
- ↑ 18.0 18.1 Robling M et al The effect of the Talking Diabetes consulting skills intervention on glycaemic control and quality of life in children with type 1 diabetes: cluster randomised controlled trial (DEPICTED study) BMJ 2012;344:e2359 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22539173 <Internet> http://www.bmj.com/content/344/bmj.e2359
Snoek FJ Self management education and good professional consultation skills for patients with diabetes BMJ 2012;344:e2673 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22539175 <Internet> http://www.bmj.com/content/344/bmj.e2673 - ↑ 19.0 19.1 ARUP Consult: Diabetes Mellitus deprecated reference
- ↑ The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med. 1998 Apr 1;128(7):517-23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9518395
- ↑ 21.0 21.1 Temple MY, Bar-Or O, Riddell MC. The reliability and repeatability of the blood glucose response to prolonged exercise in adolescent boys with IDDM. Diabetes Care. 1995 Mar;18(3):326-32. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7555475
- ↑ 22.0 22.1 Chiang JL et al Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association. Diabetes Care. June 16, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24935775 <Internet> http://care.diabetesjournals.org/content/early/2014/06/09/dc14-1140.full.pdf+html
- ↑ Larkin ME et al. Musculoskeletal complications in type 1 diabetes. Diabetes Care 2014 Jul; 37:1863 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24722493 <Internet> http://care.diabetesjournals.org/content/37/7/1863
- ↑ 24.0 24.1 Pagliuca FW et al. Generation of functional human pancreatic beta cells in vitro. Cell 2014 Oct 9; 159:428 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25303535
- ↑ 25.0 25.1 Lind M et al Glycemic Control and Excess Mortality in Type 1 Diabetes. N Engl J Med 2014; 371:1972-1982. November 20, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25409370 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1408214
- ↑ 26.0 26.1 26.2 26.3 26.4 American Diabetes Association Standards of Medical Care in Diabetes-2015: Summary of Revisions Diabetes Care. Jan 2015. 38:S1-S2 http://care.diabetesjournals.org/content/38/Supplement_1
- ↑ 27.0 27.1 27.2 27.3 27.4 Livingstone SJ et al Estimated Life Expectancy in a Scottish Cohort With Type 1 Diabetes, 2008-2010. JAMA. 2015;313(1):37-44 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25562264 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2088852
Writing Group for the DCCT/EDIC Research Group Association Between 7 Years of Intensive Treatment of Type 1 Diabetes and Long-term Mortality. JAMA. 2015;313(1):45-53 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25562265 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2088851
Katz M, Laffel L Mortality in Type 1 Diabetes in the Current Era. Two Steps Forward, One Step Backward. JAMA. 2015;313(1):35-36. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25562263 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2088833 - ↑ 28.0 28.1 Huxley RR et al Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. The Lancet Diabetes & Endocrinology. Feb 5, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25660575 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2814%2970248-7/abstract
- ↑ 29.0 29.1 Steineck I et al Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study. BMJ 2015;350:h3234 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26100640 <Internet> http://www.bmj.com/content/350/bmj.h3234
- ↑ 30.0 30.1 Libman IM et al. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: A randomized clinical trial. JAMA 2015 Dec 1; 314:2241 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26624824
- ↑ Nathan DM; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014;37(1):9-16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24356592 Free PMC Article
- ↑ 32.0 32.1 Vegas AJ et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 2016 Mar; 22:306. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26808346
Tang Q, Desai TA. Approaching a cure for type 1 diabetes. Nat Med 2016 Mar; 22:236 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26937617 - ↑ 33.0 33.1 Kuhadiya ND, Ghanim H, Mehta A et al Dapagliflozin as Additional Treatment to Liraglutide and Insulin in Patients With Type 1 Diabetes. J Clin Endocrinol Metab 101: August, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27490915 <Internet> http://press.endocrine.org/doi/pdf/10.1210/jc.2016-1451
- ↑ Varanasi A, Bellini N, Rawal D, Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011 Jul;165(1):77-84. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21646283 Free Article
- ↑ 35.0 35.1 35.2 35.3 35.4 Colberg SR, Sigal RJ, Yardley JE et al Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care 2016 Nov; 39(11): 2065-2079 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27926890 <Internet> http://care.diabetesjournals.org/content/39/11/2065
- ↑ 36.0 36.1 Beck RW, Riddlesworth T, Ruedy K et al Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections. The DIAMOND Randomized Clinical Trial. JAMA. 2017;317(4):371-378 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28118453 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2598770
Lind M, Polonsky W, Hirsch IB et al Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections. The GOLD Randomized Clinical Trial. JAMA. 2017;317(4):379-387 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28118454 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2598771
Davidson MB Continuous Glucose Monitoring in Patients With Type 1 Diabetes Taking Insulin Injections. JAMA. 2017;317(4):363-364 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28118435 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2598751 - ↑ 37.0 37.1 Riddell MC, Gallen IW, Smart CE et al Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes & Endocrinology. Jan 23, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28126459 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587(17)30014-1/fulltext
- ↑ 38.0 38.1 38.2 The REPOSE Study Group Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE). BMJ 2017;356:j1285 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28360027 Free full text <Internet> http://www.bmj.com/content/356/bmj.j1285
- ↑ 39.0 39.1 39.2 Monaco K Metformin No Help for Atherosclerosis in T1D. Findings don't support metformin in long-standing type 1 diabetes. MedPage Today. June 13, 2017 https://www.medpagetoday.com/MeetingCoverage/ADA/65999
- ↑ 40.0 40.1 Lane W, Bailey TS, Gerety G et al Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes. The SWITCH 1 Randomized Clinical Trial. JAMA. 2017;318(1):33-44 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28672316 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2635629
- ↑ 41.0 41.1 41.2 41.3 41.4 41.5 41.6 41.7 41.8 Chamberlain JJ, Kalyani RR, Leal S et al. Treatment of type 1 diabetes: Synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med 2017 Sep 12 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28892816 <Internet> http://annals.org/aim/article/2653838/treatment-type-1-diabetes-synopsis-2017-american-diabetes-association-standards
- ↑ 42.0 42.1 Karges B, Schwandt A, Heidtmann B et al Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes. JAMA. 2017;318(14):1358-1366 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29049584 https://jamanetwork.com/journals/jama/article-abstract/2656808
- ↑ 43.0 43.1 Marcovecchio ML, Chiesa ST, Bond S et al. ACE inhibitors and statins in adolescents with type 1 diabetes. N Engl J Med 2017 Nov 2; 377:1733. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29091568
- ↑ 44.0 44.1 Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group. Effect of oral insulin on prevention of diabetes in relatives of patients with type 1 diabetes: A randomized clinical trial. JAMA 2017 Nov 21; 318:1891 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29164254
- ↑ 45.0 45.1 Hooper P, Boucher MC, Cruess A, et al. Excerpt from the Canadian Ophthalmological Society evidence- based clinical practice guidelines for the management of diabetic retinopathy. Can J Ophthalmol. 2017 Nov;52 Suppl 1:S45-S74 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29074014 <Internet> http://www.canadianjournalofophthalmology.ca/article/S0008-4182(17)31047-5/fulltext
- ↑ 46.0 46.1 Heinemann L, Freckmann G, Ehrmann D et al. Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): A multicentre, randomised controlled trial. Lancet 2018 Feb 16; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29459019
Bergenstal RM. Continuous glucose monitoring: Transforming diabetes management step by step. Lancet 2018 Feb 16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29459022 - ↑ Chamberlain JJ, Johnson EL, Leal S et al. Cardiovascular Disease and Risk Management: Review of the American Diabetes Association Standards of Medical Care in Diabetes 2018. Ann Intern Med 2018 Apr 3; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29610837 <Internet> http://annals.org/aim/fullarticle/2677350/cardiovascular-disease-risk-management-review-american-diabetes-association-standards-medical
- ↑ 48.0 48.1 Lennerz BS, Barton A, Bernstein RK et al Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics. May 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29735574 <Internet> http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2017-3349
Runge C, Lee JM. How Low Can You Go? Does Lower Carb Translate to Lower Glucose? Pediatrics. May 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29735572 <Internet> http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2018-0957 - ↑ 49.0 49.1 Phend C, TB Vaccine for T1D Study Stirs Controversy. Long-term data suggest BCG vaccine may alter immune attack. MedPage Today. June 25, 2018 https://www.medpagetoday.com/meetingcoverage/ada/73696
Kuhtreiber W, et al Repeat BCG vaccination creates lasting reductions of HbA1c in subjects with long-term type 1 diabetes - long-term clinical trial follow-up. American Diabetes Association (ADA) 2018; Abstract 109-LB - ↑ 50.0 50.1 Ludvigsson JF, Neovius M, Soderling J et al Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden. BMJ 2018;362:k2638 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29976596 Free PMC Article https://www.bmj.com/content/362/bmj.k2638
- ↑ 51.0 51.1 Rawshani A et al Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 392:(10146) 477-486, August 11, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30129464 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31506-X/fulltext
- ↑ 52.0 52.1 Ovalle F, Grimes T, Xu G et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med 2018 Aug; 24:1108. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29988125 https://www.nature.com/articles/s41591-018-0089-4
- ↑ 53.0 53.1 The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018 Aug 26; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30146931 Free Article https://www.nejm.org/doi/10.1056/NEJMoa1804988
- ↑ 54.0 54.1 The ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus N Engl J Med 2018 Aug 26; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30146932 Free Article https://www.nejm.org/doi/10.1056/NEJMoa1804989
- ↑ Roglic G, Norris SL Medicines for Treatment Intensification in Type 2 Diabetes and Type of Insulin in Type 1 and Type 2 Diabetes in Low-Resource Settings: Synopsis of the World Health Organization Guidelines on Second- and Third-Line Medicines and Type of Insulin for the Control of Blood Glucose Levels in Nonpregnant Adults With Diabetes Mellitus. Ann Intern Med. 2018. Sept 4. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30178023 <Internet> http://annals.org/aim/fullarticle/2698900/medicines-treatment-intensification-type-2-diabetes-type-insulin-type-1
Humphrey LL, Kansagara D, Qaseem A. World Health Organization Guidelines on Medicines for Diabetes Treatment Intensification: Commentary From the American College of Physicians High Value Care Committee. Ann Intern Med. 2018. Sept 4. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30178054 <Internet> http://annals.org/aim/article-abstract/2698899/world-health-organization-guidelines-medicines-diabetes-treatment-intensification-commentary-from - ↑ 56.0 56.1 Antvorskov JC, Halldorsson TI, Josefsen K et al Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark. BMJ 2018;362:k3547 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30232082 Free full text https://www.bmj.com/content/362/bmj.k3547
Miettinen ME, Virtanen SM Dietary gluten and type 1 diabetes BMJ 2018;362:k3867 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30232119 https://www.bmj.com/content/362/bmj.k3867 - ↑ 57.0 57.1 Musso G, Gambino R, Cassader M, Paschetta E. Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: Meta-analysis of randomised controlled trials. BMJ 2019 Apr 9; 365:l1328. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30967375 Free Article https://www.bmj.com/content/365/bmj.l1328
- ↑ 58.0 58.1 58.2 Chamberlain JJ, Doyle-Delgado K, Peterson L, Skolnik N. Diabetes Technology: Review of the 2019 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2019. Aug 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31404925 https://annals.org/aim/fullarticle/2748278/diabetes-technology-review-2019-american-diabetes-association-standards-medical-care
- ↑ 59.0 59.1 Lowry F The Best Statins to Lower Non-HDL Cholesterol in Diabetes? Medscsape. April 13, 2022 https://www.medscape.com/viewarticle/972109
Hodkinson A, Tsimpida D, Kontopantelis E et al Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis. BMJ 2022;376:e067731 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35331984 PMCID: PMC8943592 Free PMC article https://www.bmj.com/content/376/bmj-2021-067731 - ↑ 60.0 60.1 Lou N FDA Approves First Drug to Delay Onset of Type 1 Diabetes. Teplizumab will not be subject to a risk evaluation and mitigation strategy program, after all. MedPage Today November 18, 2022 https://www.medpagetoday.com/endocrinology/type1diabetes/101823
- ↑ 61.0 61.1 61.2 Tucker ME ADA Advises New BP, Lipid Targets for People With Diabetes. Medscape. Dec 13, 2022 https://www.medscape.com/viewarticle/985482
ElSayed NA, Aleppo G, Aroda VR et al Standards of Care in Diabetes - 2023 Diabetes Care. 2023. 46(S1-S2) Jan https://diabetesjournals.org/care/issue/46/Supplement_1 - ↑ 62.0 62.1 62.2 Forlenza GP, McVean J, Beck RW et al Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes. A Randomized Clinical Trial. JAMA. Published online February 24, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36826844 https://jamanetwork.com/journals/jama/fullarticle/2801974
McVean J, Forlenza GP, Beck RW et al Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes. A Randomized Clinical Trial. JAMA. 2023;329(12):980-989 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36826834 PMCID: PMC9960023 (available on 2023-08-24) https://jamanetwork.com/journals/jama/fullarticle/2801975 - ↑ 63.0 63.1 Edwards K et al. Clinical and safety outcomes with GLP-1 receptor agonists and SGLT2 inhibitors in type 1 diabetes: A real-world study. J Clin Endocrinol Metab 2023 Apr; 108:920 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36268825 https://academic.oup.com/jcem/article-abstract/108/4/920/6765301
- ↑ 64.0 64.1 Riddell MC et al. Examining the acute glycemic effects of different types of structured exercise sessions in type 1 diabetes in a real-world setting: The Type 1 Diabetes and Exercise Initiative (T1DEXI). Diabetes Care 2023 Apr 1; 46:704. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36795053 PMCID: PMC10090894 Free PMC article https://diabetesjournals.org/care/article/46/4/704/148382/Examining-the-Acute-Glycemic-Effects-of-Different
- ↑ 65.0 65.1 65.2 NEJM Knowledge+ Endocrinology
- ↑ 66.0 66.1 Wagner S et al. Upper-extremity impairments in type 1 diabetes: Results from a controlled nationwide study. Diabetes Care 2023 Jun; 46:1204. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37000698 https://diabetesjournals.org/care/article-abstract/46/6/1204/148665/Upper-Extremity-Impairments-in-Type-1-Diabetes
- ↑ 67.0 67.1 67.2 67.3 67.4 Fang M et al. Age at diagnosis in U.S. adults with type 1 diabetes. Ann Intern Med 2023 Sep 26; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/37748184 https://www.acpjournals.org/doi/10.7326/M23-1707
- ↑ Type 1 Diabetes. Less Guesswork. More Freedom. Better Health. http://www.dafne.uk.com/disclaimer.php
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