DCCT overview
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This document summarizes a randomized controlled trial that studied the effects of intensive versus conventional diabetes therapy in 1441 patients with type 1 diabetes between 1983-1989. The trial had two arms - a primary prevention arm of patients with diabetes for 1-5 years and no complications, and a secondary prevention arm of patients with diabetes for 1-15 years and some retinopathy or nephropathy. The intensive therapy group achieved significantly lower average blood glucose and HbA1c levels. In both prevention arms, intensive therapy reduced the risk of retinopathy, nephropathy, and neuropathy compared to conventional therapy, with risk reductions ranging from 34-76%. However, intensive therapy also led to higher rates of hypoglycemia.
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DCCT - HypoglycemiaPeninsulaEndocrine The DCCT trial compared intensive versus conventional diabetes treatment in 1,441 patients with type 1 diabetes from 1983 to 1989. The intensive group aimed for tighter blood glucose control through multiple daily insulin injections or pump therapy and frequent self-monitoring. This led to significantly more frequent hypoglycemic events compared to the conventional group, who followed a less strict regimen. Over the course of the trial, the intensive group experienced over 3 times as many hypoglycemic events and over 3 times the risk of hypoglycemic coma or seizure. However, intensive control also demonstrated long-term benefits in reducing diabetes complications.
DCCT Landmark Trial
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The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-term Complications in Insulin Dependent Diabetes Mellitus
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DCCT Learned LessonsMohammad Othman Daoud The 30+ year DCCT-EDIC trial provided important insights into the long-term effects of intensive glycemic control in type 1 diabetes patients. The DCCT found that intensive control significantly reduced the risk of developing diabetic complications compared to conventional treatment. The EDIC observational follow-up study found these benefits were durable, and intensive control continued to have beneficial effects on complications even after glycemic control was relaxed. Together, DCCT-EDIC established intensive glycemic control as the standard of care for type 1 diabetes and demonstrated its benefits in both preventing and delaying complications over the long term.
DCCT – intensive diabetes therapy and glomerular filtration
DCCT – intensive diabetes therapy and glomerular filtrationPeninsulaEndocrine The DCCT trial compared intensive diabetes therapy to conventional therapy in patients with type 1 diabetes over 22 years. Intensive therapy aimed to achieve an HbA1c level below 6.05% using three or more daily insulin injections or an insulin pump. Conventional therapy aimed to prevent symptoms of hyper/hypoglycemia with one-two daily injections. The trial found intensive therapy reduced the risk of impaired glomerular filtration rate (GFR) by 50% and end-stage renal disease by 50% compared to conventional therapy. Intensive therapy also slowed later GFR decline and increased mean GFR levels. The benefits were fully explained by lower HbA1c and albumin excretion from intensive therapy.
DCCT
DCCTIsabella Nga Lai The Diabetes Control and Complications Trial (DCCT) was a landmark randomized controlled trial that demonstrated intensive insulin therapy can significantly reduce the risk of microvascular complications in patients with type 1 diabetes compared to conventional insulin therapy. The DCCT studied 1441 patients over 6.5 years and found intensive therapy reduced the risk of retinopathy by 76%, microalbuminuria by 34%, and clinical neuropathy by 69%. However, intensive therapy also increased the risk of hypoglycemia and weight gain. The study did not find a difference in macrovascular events or mortality between the treatment groups.
UKPDS overview
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UKPDS
UKPDSIsabella Nga Lai 1) The UKPDS trial compared intensive blood glucose control using sulfonylureas or insulin to conventional treatment in over 3,800 patients with newly diagnosed type 2 diabetes over 10 years.
2) Intensive treatment lowered A1C more but did not reduce macrovascular complications like heart disease. It did reduce microvascular complications like eye and kidney disease.
3) Intensive treatment was associated with more hypoglycemia.
ADVANCE - Type 2 diabetes - vascular risk with intervention
ADVANCE - Type 2 diabetes - vascular risk with interventionPeninsulaEndocrine This document summarizes a study that investigated the effects of intensive blood glucose control versus standard control in patients over age 55 with type 2 diabetes. Over 5 years of follow up, intensive control reduced the risk of major macrovascular and microvascular events by 10% compared to standard control. Intensive control also significantly reduced new or worsening nephropathy and new-onset microalbuminuria. However, it increased the risk of severe and minor hypoglycemia. The study found no difference in all-cause or cardiovascular mortality between the intensive and standard control groups.
DCCT/EDIC - Type 1 diabetes - cardiovascular risk with intervention
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UKPDS - 10 year follow up
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Landmark trials in diabetes
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ACCORD
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Clinical Trials for Diabetes
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RABBIT 2
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A pragmatic framework for what the non-Endocrinology Doctor should do with these drugs whilst the patient is in, and being discharged from, the Intensive Care Unit.
An outline of current trials evaluating glycaemia in the Intensive Care Unit.
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Gestational diabetes
Gestational diabetesPeninsulaEndocrine Gestational diabetes (GDM) is glucose intolerance first identified during pregnancy. Risk factors include BMI over 30, previous large or diabetic baby, family history of diabetes. GDM is identified through a 75g oral glucose tolerance test. It is associated with risks like large baby, shoulder dystocia, preeclampsia. Treatment like insulin lowers risks. Other types of diabetes may present as GDM and require identification. Mild maternal hyperglycemia increases risks incrementally without a clear threshold.
Endocrine disease in pregnancy
Endocrine disease in pregnancyPeninsulaEndocrine This document discusses the management of various endocrine diseases in pregnancy, including hypothyroidism, hyperthyroidism, prolactinoma, and Addison's disease. It provides guidance on treatment, monitoring, risks of under-treatment, and complications for each condition. Case examples are presented and management strategies are outlined, emphasizing the importance of optimizing treatment to reduce risks while minimizing harm to the mother and fetus. Close monitoring is recommended for conditions like Graves' disease and prolactinoma.
Diabetes in pregnancy
Diabetes in pregnancyPeninsulaEndocrine This document discusses diabetes in pregnancy, including:
- Risks to the mother include acceleration of complications like eye and kidney disease, as well as risks of hypoglycemia, pre-eclampsia, and obstetric complications.
- Risks to the fetus include congenital malformations, macrosomia, stillbirth, neonatal death, and issues like hypoglycemia and jaundice after birth.
- Management involves tight glycemic control, aspirin, monitoring for complications, and delivery planning based on gestational age and fetal growth. Acute issues like hypoglycemia and diabetic ketoacidosis require prompt treatment.
Hypoglycaemia in older people
Hypoglycaemia in older peoplePeninsulaEndocrine - Hypoglycemia is more common in older adults treated with insulin or sulphonylureas and can be difficult to recognize due to non-specific symptoms. Unexplained falls, unsteadiness, or nausea may indicate unrecognized hypoglycemia.
- Maintaining tight glycemic control with aggressive HbA1c targets increases hypoglycemia risk in older adults. Guidelines recommend less stringent HbA1c targets for older patients based on functional status and comorbidities.
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Diabetes in the elderly
Diabetes in the elderlyPeninsulaEndocrine This document discusses diabetes management in the elderly population. It highlights that life expectancy is lower for those with type 1 diabetes compared to those without. A study on elderly patients who received awards for long-term diabetes found identifiers of long survival included reasonable blood sugar control, normal weight, and being non-smokers. Guidelines recommend individualized care plans for elderly patients in care homes that are agreed upon by the patient, doctor, and home staff. An audit found that some care home staff lacked diabetes education and homes did not always have policies for treating low blood sugar. Management of diabetes in the elderly aims to avoid low blood sugar, control symptoms, and reduce risks of infection and hospitalization.
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Primary hyperaldosteronism - arterial venous sampling casesPeninsulaEndocrine This document discusses three patient cases presenting with resistant hypertension. Case 1 involves a 49-year-old female with obesity and resistant hypertension who shows signs of primary aldosteronism based on blood tests. Case 2 is a 53-year-old female with a 10-year history of resistant hypertension, low potassium levels, and imaging showing a lesion on her left adrenal gland. Case 3 is a 55-year-old male with resistant hypertension and normal potassium who was confirmed to have primary aldosteronism based on salt loading tests, but no adrenal lesion was seen on imaging. All three patients underwent adrenal vein sampling to further evaluate their condition.
Calcium metabolism handout
Calcium metabolism handoutPeninsulaEndocrine This document summarizes the key components involved in vitamin D and calcium homeostasis, including the roles of vitamin D, parathyroid hormone (PTH), and calcitonin. It discusses how vitamin D is obtained from sunlight or diet and activated in the body. PTH and calcitonin work in opposition to regulate calcium levels - PTH increases calcium levels by acting on the kidneys and bone, while calcitonin decreases calcium levels by inhibiting bone resorption. PTH and vitamin D also interact, as vitamin D helps absorb calcium from the gut and PTH stimulates its production. Together this maintains appropriate calcium and phosphate levels in the blood and body.
Calcium metabolism handout
Calcium metabolism handoutPeninsulaEndocrine This document discusses calcium homeostasis and disorders, including hypercalcemia and hyperparathyroidism. It provides details on the roles of parathyroid hormone (PTH), vitamin D, and calcitonin in regulating calcium levels. It examines causes of hypercalcemia such as primary hyperparathyroidism, malignancy, and vitamin D toxicity. Guidelines for treatment of asymptomatic primary hyperparathyroidism with surgery or medication are reviewed based on calcium levels, bone mineral density, kidney stones, and age. Non-surgical treatments including vitamin D supplementation and cinacalcet are also discussed.
Kallmann syndrome
Kallmann syndromePeninsulaEndocrine The document discusses delayed puberty, defined as the absence or incomplete development of secondary sex characteristics past a certain age. It then focuses on hypogonadotrophic hypogonadism, which affects about 1 in 10,000 male births and can be associated with loss of smell. Sixteen gene defects have been linked to Kallmann syndrome. Short term goals of treatment include attaining appropriate sexual development and growth, while long term goals include maintaining normal hormone levels and inducing fertility. Pretreatment with FSH before GnRH therapy has shown promise in inducing testicular growth and fertility in men with congenital hypogonadotropic hypogonadism and underdeveloped testes.
Kallmann syndrome
Kallmann syndromePeninsulaEndocrine The document discusses delayed puberty, defined as the absence or incomplete development of secondary sex characteristics past a certain age. It then focuses on hypogonadotrophic hypogonadism, which affects about 1 in 10,000 male births and can be associated with loss of smell. Sixteen gene defects have been linked to Kallmann syndrome. Short term goals of treatment include attaining appropriate sexual development and growth, while long term goals include maintaining normal hormone levels and inducing fertility. Pretreatment with FSH before GnRH therapy has shown promise in inducing testicular growth and fertility in men with congenital hypogonadotropic hypogonadism and underdeveloped testes.
Hypogonadism and testosterone replacement part 2
Hypogonadism and testosterone replacement part 2PeninsulaEndocrine The FDA is investigating the risks of stroke, heart attack, and death in men taking testosterone products due to two recent studies suggesting increased cardiovascular risks. While the FDA has not concluded testosterone treatment definitively increases these risks, they are reassessing the safety issue. The FDA advises patients to discuss concerns with their healthcare providers and for providers to consider if benefits outweigh potential risks. Testosterone is only approved to treat medical conditions causing low levels like testicular or hypothalamic-pituitary problems.
Hypogonadism and testosterone replacement
Hypogonadism and testosterone replacementPeninsulaEndocrine This document discusses hypogonadism and testosterone replacement. It provides information on:
- The causes and clinical presentation of primary and secondary hypogonadism.
- Diagnosing hypogonadism through patient history, physical exam, and measuring serum testosterone and other hormone levels.
- Goals of testosterone replacement therapy in treating symptoms and restoring physiological functions.
- Various treatment options for testosterone replacement therapy including oral, buccal, implant, patch, gel, and intramuscular injection formulations. It provides details on the administration and pharmacokinetics of these different options.
Erectile dysfunction in diabetes
Erectile dysfunction in diabetesPeninsulaEndocrine Erectile dysfunction is common in men with diabetes and tends to be more severe than in non-diabetic men. Screening for ED should be conducted annually as part of diabetes reviews. Asking direct questions such as "Are your erections hard enough for penetration?" can help identify cases of ED. Phosphodiesterase type 5 inhibitors are usually first-line treatment but some men may require additional options or a dose change if initial treatment is not effective. Testosterone deficiency can also contribute to ED in diabetic men.
The role of the podiatrist
The role of the podiatristPeninsulaEndocrine The podiatrist plays an important role in assessing risk and treating foot complications in patients with diabetes. Key responsibilities include performing vascular, neurological, and wound assessments; providing debridement and dressing of ulcers; addressing biomechanical issues; and ensuring proper offloading. The podiatrist works as part of a multidisciplinary team to educate patients, treat foot problems, and prevent amputations through a holistic approach to diabetic foot care.
The diabetic foot
The diabetic footPeninsulaEndocrine This document discusses diabetic foot care and prevention of amputations. It notes that amputations due to diabetes account for significant NHS costs and resources. While up to 80% of amputations are preventable, amputation rates vary widely across the UK. The document examines factors contributing to high amputation rates in some areas like Devon, and opportunities to improve care through measures like the Ipswich Touch Test for inpatient foot screening and better coordination between primary and secondary care. Overall it emphasizes the importance of preventing foot complications in diabetes which can greatly reduce quality of life.
Pituitary disease
Pituitary diseasePeninsulaEndocrine This document discusses the presentation, testing, and management of pituitary adenomas and hypothalamic syndromes. It provides guidance on testing a 66-year-old man with a confirmed pituitary adenoma discovered on MRI after presenting with stroke symptoms. Testing strategies and their limitations are reviewed. Factors affecting decisions around intervention and appropriate follow-up strategies are also discussed, drawing on literature to support recommendations. Long-term management of patients with prolactinomas on dopamine agonists is explored, including monitoring, treatment withdrawal, and surveillance of side effects.
Adrenocortical tumours
Adrenocortical tumoursPeninsulaEndocrine - Adrenocortical tumors are rare cancers that often present without specific symptoms and with delays in diagnosis and treatment planning.
- All five patients experienced delays at various points from initial presentation to surgery and initiation of mitotane treatment.
- Mitotane was started in all patients but therapeutic levels were only achieved in one patient, with the others either managing subtherapeutic levels or dying before achieving therapeutic levels.
- Improving awareness of these rare tumors and expediting referrals, multidisciplinary team decision making, and starting adjuvant treatment could help reduce delays but may not overcome the tumors' poor prognosis.
Adrenal Incidentalomas
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Macrovascular disease in diabetes
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DCCT overview
- 2. 1441 pt with T1DM Secondary Prevention Primary Prevention n=726 Conventional therapy n=378 • • • • • Intensive therapy n=348 n=715 Conventional therapy n=352 Intensive therapy n=363 Randomised, multicentre trial 1441 pts recruited from 29 centres 1983-89 Av follow-up was 6.5 yrs (mean 3-9) Inclusion age 13-39 yrs, Type 1 DM Primary prevention arm – 1-5 yrs DM, no retinopathy or nephropathy • Secondary prevention arm – 1-15yrs DM, M NPRetinopathy, Ur Microalb <200mg/24 hrs
- 3. Glycemic control 16.6 13.8 11.1 8.3 5.5 • HbA1c improvement in intensive vs. conventional treated group (p0.001) • Mean glucose level 8.6mmol/l vs. 12.8mmol/l (p<0.001)
- 4. Retinopathy • Primary prevention group (Intensive vs. conventional) – 23 vs 91 pts developed retinopathy in 6 years followup (Mean risk reduction 76%) • Secondary prevention group (Intensive vs. conventional) – 77 vs 143 pts developed progressive retinopathy (Mean risk reduction 54%) – 47% reduction of severe retinopathy, 56% reduction in laser photocoagulation • Transient worsening of retinopathy (22% vs. 13%) 18 months
- 5. Nephropathy • Primary prevention group – Mean risk reduction for microalbuminuria by 34% (p 0.04) intensive gp • Secondary prevention group – Mean risk reduction for microalbuminuria by 43% (p 0.001) intensive gp • Risk reduction in albuminuria (54%) and microalbunimuria (39%) in intensive treatment arms
- 6. Neuropathy • Primary Prevention group – 3% vs 10% developed neuropathy (69% reduction of neuropathy by 5 years, p0.006) • Secondary Prevention group – 7% vs 16% developed neuropathy (57% reduction of neuropathy by 5 years)
- 7. Secondary analysis • • • • • • • Severe hypoglycemic episodes 62 vs. 19/100 pt yrs Hypoglycemia Coma / seizure episodes 16 vs. 5/100 pt yrs Hospitalisation 54/40 pts vs. 36/27 pts Major accidents 20 vs. 22 (2 fatalities, 1 vs. 1) No difference in neuropsycholgical function No death, MI or stroke Wt gain ( overweight 12.7 vs. 9.3 /100 pt yrs)