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○ Diabetes without typical features of type 1 or type 2 diabetes (negative diabetes-associated autoantibodies, nonobese, lacking other metabolic features, especially with strong family history of diabetes)

○ Stable, mild fasting hyperglycemia (100–150 mg/dL [5.5–8.5 mmol/L]), stable A1C between 5.6 and 7.6% (between 38 and 60 mmol/mol), especially if nonobese


Cystic fibrosis–related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis, occurring in about 20% of adolescents and 40–50% of adults. Diabetes in this population, compared with individuals with type 1 or type 2 diabetes, is associated with worse nutritional status, more severe inflammatory lung disease, and greater mortality. Insulin insufficiency is the primary defect in CFRD. Genetically determined β-cell function and insulin resistance associated with infection and inflammation may also contribute to the development of CFRD. Milder abnormalities of glucose tolerance are even more common and occur at earlier ages than CFRD. Whether individuals with IGT should be treated with insulin replacement has not currently been determined. Although screening for diabetes before the age of 10 years can identify risk for progression to CFRD in those with abnormal glucose tolerance, no benefit has been established with respect to weight, height, BMI, or lung function. Continuous glucose monitoring or HOMA of β-cell function ( Wholesale Online Sale Good Selling Womens Samantha Slim Jeans Narrow Leg His Sale Discounts PjoAt
) may be more sensitive than OGTT to detect risk for progression to CFRD; however, evidence linking these results to long-term outcomes is lacking, and these tests are not recommended for screening ( 91 ).

CFRD mortality has significantly decreased over time, and the gap in mortality between cystic fibrosis patients with and without diabetes has considerably narrowed ( 92 ). There are limited clinical trial data on therapy for CFRD. The largest study compared three regimens: premeal insulin aspart, repaglinide, or oral placebo in cystic fibrosis patients with diabetes or abnormal glucose tolerance. Participants all had weight loss in the year preceding treatment; however, in the insulin-treated group, this pattern was reversed, and patients gained 0.39 (± 0.21) BMI units ( 0.02). The repaglinide-treated group had initial weight gain, but this was not sustained by 6 months. The placebo group continued to lose weight ( Womens Viport L/S Shirt Blouse Vila Cheap Purchase Fast Delivery pgU3j
). Insulin remains the most widely used therapy for CFRD ( 94 ).

Additional resources for the clinical management of CFRD can be found in the position statement “Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes: A Position Statement of the American Diabetes Association and a Clinical Practice Guideline of the Cystic Fibrosis Foundation, Endorsed by the Pediatric Endocrine Society” ( 95 ) and in the International Society for Pediatric and Adolescent Diabetes’s 2014 clinical practice consensus guidelines ( 96 ).

Annual screening for cystic fibrosis related diabetes with oral glucose tolerance test should begin by age 10 years in all patients with cystic fibrosis not previously diagnosed with cystic fibrosis–related diabetes. B

Borrelia burgdorferi –specific IgG and IgM scoring is based on the presence of at least 5 out of a possible 10 diagnostic IgG bands and 2 of a possible 3 IgM bands following reaching the threshold of a positive or equivocal screening EIA [ 248 ]. The IgM blot is not clinically meaningful in patients who present 30 days or longer after symptom onset due to high rates of false positivity. Additionally, seropositivity for both IgM- and IgG-class antibodies to LD-associated Borrelia spp may persist for months to years (>10–15 years) following resolution of the infection [ 249 ]. Since positivity by the TTTA may reflect remote exposure rather than current infection, it is recommended that only symptomatic patients with an appropriate exposure history be tested for LD. Finally, multiple LD “specialty” laboratories have emerged in recent years, claiming expertise in tick-borne disease diagnosis and offering LD diagnostic assays with improved sensitivity [ 250 , 251 ]. These laboratories may not be CLIA-approved and offer LD diagnostic assays using methods and interpretive criteria for which validation data has neither been made publically available nor been vetted by high-quality peer review. Submission of patient specimens to such laboratories is not recommended.

Classical relapsing fever transmitted by the bites of soft (argasid) ticks burdens residents or travelers to mainly the western United States, although sporadic cases occur in the south-central states. Louse-borne relapsing fever is endemic to tropical countries or may become epidemic in refugee camps; travelers would be the only patients who might present with louse-borne relapsing fever, and their diagnosis would be similar to that for tick-borne relapsing fever. Relapsing fever presents as recurrent fevers of several days’ duration, terminating with crisis and resuming after a few days; febrile episodes are marked by the presence of large numbers of spirochetes in the peripheral blood. Relapsing fever-like borreliae ( B. miyamotoi ) transmitted by the same hard tick as that transmitting the agents of LD cause fever that has a less characteristic presentation and may be confused with human granulocytic anaplasmosis; spirochetes are sparse in peripheral blood but are usually detectable by NAAT (particularly reverse-transcription PCR [RT-PCR]). Recent data suggest that both acute and convalescent sera from patients with B. miyamotoi infection are frequently reactive by first-tier serologic assays for LD (eg, C6 EIA) and convalescent sera may be positive of B. burgdorferi– specific IgM blots [ 252 ]. Despite this, testing for B. miyamotoi infection using B. burgdorferi serologic assays is not recommended.

In the United States, rickettsial diseases that are transmitted by ticks include Rocky Mountain spotted fever (RMSF) due to Rickettsia rickettsii ; “mild” RMSF ( Rickettsia parkeri and other spotted fever group Rickettsia spp), human granulocytic anaplasmosis ( Anaplasma phagocytophilum ), human monocytic ehrlichiosis ( Ehrlichia chaffeensis ), and ehrlichiosis caused by Ehrlichia ewingii or Ehrlichia muris [ 253 , 254 ]. Although clinically similar, these diseases are epidemiologically and etiologically distinct illnesses. Endemic typhus and flea-borne typhus ( Rickettsia typhi and Rickettsia felis , respectively) may also infect people in the United States, mainly in warmer sites where fleas are common throughout the year. Rare epidemic typhus ( Rickettsia prowazekii ) cases have been recorded in the United States from contact with flying squirrels or their nests. Rickettsialpox ( Rickettsia akari ), comprising a mild febrile disease with rash and eschar, is maintained by mouse mites in many large urban areas. The diagnosis of patients with these infections is challenging early in the course of their clinical infection since signs and symptoms are often nonspecific or mimic benign viral illnesses. Rash is usually present in most acute rickettsiosis, but skin color may prevent its recognition. The likelihood of severe morbidity or mortality with delaying treatment for RMSF means that patients should be presumptively treated without waiting for laboratory confirmation, which rests mainly on seroconversion.

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